Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans

Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Juliane Russlies [verfasserIn] Anke Fähnrich [verfasserIn] Mareike Witte [verfasserIn] Junping Yin [verfasserIn] Sandrine Benoit [verfasserIn] Regine Gläser [verfasserIn] Claudia Günter [verfasserIn] Rüdiger Eming [verfasserIn] Jeanette Erdmann [verfasserIn] Damian Gola [verfasserIn] Yask Gupta [verfasserIn] Maike Marleen Holtsche [verfasserIn] Johannes S. Kern [verfasserIn] Inke R. König [verfasserIn] Dimitra Kiritsi [verfasserIn] Wolfgang Lieb [verfasserIn] Christian D. Sadik [verfasserIn] Miklós Sárdy [verfasserIn] Franziska Schauer [verfasserIn] Nina van Beek [verfasserIn] Anke Weidinger [verfasserIn] Margitta Worm [verfasserIn] Detlef Zillikens [verfasserIn] Enno Schmidt [verfasserIn] Hauke Busch [verfasserIn] Saleh M. Ibrahim [verfasserIn] Misa Hirose [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 10(2019)
Übergeordnetes Werk:	volume:10 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2019.02200

Katalog-ID:	DOAJ03151412X

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520			\|a Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.
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700	0		\|a Johannes S. Kern \|e verfasserin \|4 aut
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700	0		\|a Wolfgang Lieb \|e verfasserin \|4 aut
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700	0		\|a Christian D. Sadik \|e verfasserin \|4 aut
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700	0		\|a Miklós Sárdy \|e verfasserin \|4 aut
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700	0		\|a Saleh M. Ibrahim \|e verfasserin \|4 aut
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700	0		\|a Misa Hirose \|e verfasserin \|4 aut
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allfields	10.3389/fimmu.2019.02200 doi (DE-627)DOAJ03151412X (DE-599)DOAJfaca4f04c86748c0ae32cd10436da09b DE-627 ger DE-627 rakwb eng RC581-607 Juliane Russlies verfasserin aut Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy Anke Fähnrich verfasserin aut Anke Fähnrich verfasserin aut Mareike Witte verfasserin aut Mareike Witte verfasserin aut Junping Yin verfasserin aut Sandrine Benoit verfasserin aut Sandrine Benoit verfasserin aut Regine Gläser verfasserin aut Regine Gläser verfasserin aut Claudia Günter verfasserin aut Claudia Günter verfasserin aut Rüdiger Eming verfasserin aut Rüdiger Eming verfasserin aut Jeanette Erdmann verfasserin aut Damian Gola verfasserin aut Yask Gupta verfasserin aut Maike Marleen Holtsche verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Inke R. König verfasserin aut Dimitra Kiritsi verfasserin aut Dimitra Kiritsi verfasserin aut Wolfgang Lieb verfasserin aut Wolfgang Lieb verfasserin aut Christian D. Sadik verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Franziska Schauer verfasserin aut Franziska Schauer verfasserin aut Nina van Beek verfasserin aut Anke Weidinger verfasserin aut Anke Weidinger verfasserin aut Margitta Worm verfasserin aut Margitta Worm verfasserin aut Detlef Zillikens verfasserin aut Detlef Zillikens verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Hauke Busch verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.02200 kostenfrei https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
spelling	10.3389/fimmu.2019.02200 doi (DE-627)DOAJ03151412X (DE-599)DOAJfaca4f04c86748c0ae32cd10436da09b DE-627 ger DE-627 rakwb eng RC581-607 Juliane Russlies verfasserin aut Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy Anke Fähnrich verfasserin aut Anke Fähnrich verfasserin aut Mareike Witte verfasserin aut Mareike Witte verfasserin aut Junping Yin verfasserin aut Sandrine Benoit verfasserin aut Sandrine Benoit verfasserin aut Regine Gläser verfasserin aut Regine Gläser verfasserin aut Claudia Günter verfasserin aut Claudia Günter verfasserin aut Rüdiger Eming verfasserin aut Rüdiger Eming verfasserin aut Jeanette Erdmann verfasserin aut Damian Gola verfasserin aut Yask Gupta verfasserin aut Maike Marleen Holtsche verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Inke R. König verfasserin aut Dimitra Kiritsi verfasserin aut Dimitra Kiritsi verfasserin aut Wolfgang Lieb verfasserin aut Wolfgang Lieb verfasserin aut Christian D. Sadik verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Franziska Schauer verfasserin aut Franziska Schauer verfasserin aut Nina van Beek verfasserin aut Anke Weidinger verfasserin aut Anke Weidinger verfasserin aut Margitta Worm verfasserin aut Margitta Worm verfasserin aut Detlef Zillikens verfasserin aut Detlef Zillikens verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Hauke Busch verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.02200 kostenfrei https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfields_unstemmed	10.3389/fimmu.2019.02200 doi (DE-627)DOAJ03151412X (DE-599)DOAJfaca4f04c86748c0ae32cd10436da09b DE-627 ger DE-627 rakwb eng RC581-607 Juliane Russlies verfasserin aut Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy Anke Fähnrich verfasserin aut Anke Fähnrich verfasserin aut Mareike Witte verfasserin aut Mareike Witte verfasserin aut Junping Yin verfasserin aut Sandrine Benoit verfasserin aut Sandrine Benoit verfasserin aut Regine Gläser verfasserin aut Regine Gläser verfasserin aut Claudia Günter verfasserin aut Claudia Günter verfasserin aut Rüdiger Eming verfasserin aut Rüdiger Eming verfasserin aut Jeanette Erdmann verfasserin aut Damian Gola verfasserin aut Yask Gupta verfasserin aut Maike Marleen Holtsche verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Inke R. König verfasserin aut Dimitra Kiritsi verfasserin aut Dimitra Kiritsi verfasserin aut Wolfgang Lieb verfasserin aut Wolfgang Lieb verfasserin aut Christian D. Sadik verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Franziska Schauer verfasserin aut Franziska Schauer verfasserin aut Nina van Beek verfasserin aut Anke Weidinger verfasserin aut Anke Weidinger verfasserin aut Margitta Worm verfasserin aut Margitta Worm verfasserin aut Detlef Zillikens verfasserin aut Detlef Zillikens verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Hauke Busch verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.02200 kostenfrei https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsGer	10.3389/fimmu.2019.02200 doi (DE-627)DOAJ03151412X (DE-599)DOAJfaca4f04c86748c0ae32cd10436da09b DE-627 ger DE-627 rakwb eng RC581-607 Juliane Russlies verfasserin aut Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy Anke Fähnrich verfasserin aut Anke Fähnrich verfasserin aut Mareike Witte verfasserin aut Mareike Witte verfasserin aut Junping Yin verfasserin aut Sandrine Benoit verfasserin aut Sandrine Benoit verfasserin aut Regine Gläser verfasserin aut Regine Gläser verfasserin aut Claudia Günter verfasserin aut Claudia Günter verfasserin aut Rüdiger Eming verfasserin aut Rüdiger Eming verfasserin aut Jeanette Erdmann verfasserin aut Damian Gola verfasserin aut Yask Gupta verfasserin aut Maike Marleen Holtsche verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Inke R. König verfasserin aut Dimitra Kiritsi verfasserin aut Dimitra Kiritsi verfasserin aut Wolfgang Lieb verfasserin aut Wolfgang Lieb verfasserin aut Christian D. Sadik verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Franziska Schauer verfasserin aut Franziska Schauer verfasserin aut Nina van Beek verfasserin aut Anke Weidinger verfasserin aut Anke Weidinger verfasserin aut Margitta Worm verfasserin aut Margitta Worm verfasserin aut Detlef Zillikens verfasserin aut Detlef Zillikens verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Hauke Busch verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.02200 kostenfrei https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsSound	10.3389/fimmu.2019.02200 doi (DE-627)DOAJ03151412X (DE-599)DOAJfaca4f04c86748c0ae32cd10436da09b DE-627 ger DE-627 rakwb eng RC581-607 Juliane Russlies verfasserin aut Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology. mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy Anke Fähnrich verfasserin aut Anke Fähnrich verfasserin aut Mareike Witte verfasserin aut Mareike Witte verfasserin aut Junping Yin verfasserin aut Sandrine Benoit verfasserin aut Sandrine Benoit verfasserin aut Regine Gläser verfasserin aut Regine Gläser verfasserin aut Claudia Günter verfasserin aut Claudia Günter verfasserin aut Rüdiger Eming verfasserin aut Rüdiger Eming verfasserin aut Jeanette Erdmann verfasserin aut Damian Gola verfasserin aut Yask Gupta verfasserin aut Maike Marleen Holtsche verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Johannes S. Kern verfasserin aut Inke R. König verfasserin aut Dimitra Kiritsi verfasserin aut Dimitra Kiritsi verfasserin aut Wolfgang Lieb verfasserin aut Wolfgang Lieb verfasserin aut Christian D. Sadik verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Miklós Sárdy verfasserin aut Franziska Schauer verfasserin aut Franziska Schauer verfasserin aut Nina van Beek verfasserin aut Anke Weidinger verfasserin aut Anke Weidinger verfasserin aut Margitta Worm verfasserin aut Margitta Worm verfasserin aut Detlef Zillikens verfasserin aut Detlef Zillikens verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Enno Schmidt verfasserin aut Hauke Busch verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.02200 kostenfrei https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
language	English
source	In Frontiers in Immunology 10(2019) volume:10 year:2019
sourceStr	In Frontiers in Immunology 10(2019) volume:10 year:2019
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Juliane Russlies @@aut@@ Anke Fähnrich @@aut@@ Mareike Witte @@aut@@ Junping Yin @@aut@@ Sandrine Benoit @@aut@@ Regine Gläser @@aut@@ Claudia Günter @@aut@@ Rüdiger Eming @@aut@@ Jeanette Erdmann @@aut@@ Damian Gola @@aut@@ Yask Gupta @@aut@@ Maike Marleen Holtsche @@aut@@ Johannes S. Kern @@aut@@ Inke R. König @@aut@@ Dimitra Kiritsi @@aut@@ Wolfgang Lieb @@aut@@ Christian D. Sadik @@aut@@ Miklós Sárdy @@aut@@ Franziska Schauer @@aut@@ Nina van Beek @@aut@@ Anke Weidinger @@aut@@ Margitta Worm @@aut@@ Detlef Zillikens @@aut@@ Enno Schmidt @@aut@@ Hauke Busch @@aut@@ Saleh M. Ibrahim @@aut@@ Misa Hirose @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ03151412X
language_de	englisch
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While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T&gt;C, m.16051A&gt;G, and m.16162A&gt;G in the D-loop region of the mtDNA, and m.11914G&gt;A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. 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callnumber-first	R - Medicine
author	Juliane Russlies
spellingShingle	Juliane Russlies misc RC581-607 misc mitochondrial DNA misc mitochondrial haplogroup misc polymorphisms misc autoimmune skin diseases misc bullous pemphigoid misc mitochondrial function misc Immunologic diseases. Allergy Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans
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topic_title	RC581-607 Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans mitochondrial DNA mitochondrial haplogroup polymorphisms autoimmune skin diseases bullous pemphigoid mitochondrial function
topic	misc RC581-607 misc mitochondrial DNA misc mitochondrial haplogroup misc polymorphisms misc autoimmune skin diseases misc bullous pemphigoid misc mitochondrial function misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc mitochondrial DNA misc mitochondrial haplogroup misc polymorphisms misc autoimmune skin diseases misc bullous pemphigoid misc mitochondrial function misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc mitochondrial DNA misc mitochondrial haplogroup misc polymorphisms misc autoimmune skin diseases misc bullous pemphigoid misc mitochondrial function misc Immunologic diseases. Allergy
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title	Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans
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title_full	Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans
author_sort	Juliane Russlies
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author_browse	Juliane Russlies Anke Fähnrich Mareike Witte Junping Yin Sandrine Benoit Regine Gläser Claudia Günter Rüdiger Eming Jeanette Erdmann Damian Gola Yask Gupta Maike Marleen Holtsche Johannes S. Kern Inke R. König Dimitra Kiritsi Wolfgang Lieb Christian D. Sadik Miklós Sárdy Franziska Schauer Nina van Beek Anke Weidinger Margitta Worm Detlef Zillikens Enno Schmidt Hauke Busch Saleh M. Ibrahim Misa Hirose
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title_sort	polymorphisms in the mitochondrial genome are associated with bullous pemphigoid in germans
callnumber	RC581-607
title_auth	Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans
abstract	Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.
abstractGer	Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.
abstract_unstemmed	Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.
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title_short	Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans
url	https://doi.org/10.3389/fimmu.2019.02200 https://doaj.org/article/faca4f04c86748c0ae32cd10436da09b https://www.frontiersin.org/article/10.3389/fimmu.2019.02200/full https://doaj.org/toc/1664-3224
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Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T&gt;C, m.16051A&gt;G, and m.16162A&gt;G in the D-loop region of the mtDNA, and m.11914G&gt;A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondrial DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondrial haplogroup</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">polymorphisms</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">autoimmune skin diseases</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">bullous pemphigoid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondrial function</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. 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Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans

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