A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity
Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or clo...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Hammer, Christian [verfasserIn] Wanitchakool, Podchanart [verfasserIn] Sirianant, Lalida [verfasserIn] Papiol, Sergi [verfasserIn] Monnheimer, Mathieu [verfasserIn] Faria, Diana [verfasserIn] Ousingsawat, Jiraporn [verfasserIn] Schramek, Natalie [verfasserIn] Schmitt, Corinna [verfasserIn] Margos, Gabriele [verfasserIn] Michel, Angelika [verfasserIn] Kraiczy, Peter [verfasserIn] Pawlita, Michael [verfasserIn] Schreiber, Rainer [verfasserIn] Schulz, Thomas F. [verfasserIn] Fingerle, Volker [verfasserIn] Tumani, Hayrettin [verfasserIn] Ehrenreich, Hannelore [verfasserIn] Kunzelmann, Karl [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Übergeordnetes Werk: |
Enthalten in: Molecular medicine - [London] : BioMed Central, 1994, 21(2015), 1 vom: Jan., Seite 26-37 |
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| Übergeordnetes Werk: |
volume:21 ; year:2015 ; number:1 ; month:01 ; pages:26-37 |
| Links: |
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| DOI / URN: |
10.2119/molmed.2014.00219 |
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| Katalog-ID: |
SPR008068607 |
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| 245 | 1 | 2 | |a A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity |
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| 520 | |a Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. | ||
| 700 | 1 | |a Wanitchakool, Podchanart |e verfasserin |4 aut | |
| 700 | 1 | |a Sirianant, Lalida |e verfasserin |4 aut | |
| 700 | 1 | |a Papiol, Sergi |e verfasserin |4 aut | |
| 700 | 1 | |a Monnheimer, Mathieu |e verfasserin |4 aut | |
| 700 | 1 | |a Faria, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Ousingsawat, Jiraporn |e verfasserin |4 aut | |
| 700 | 1 | |a Schramek, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitt, Corinna |e verfasserin |4 aut | |
| 700 | 1 | |a Margos, Gabriele |e verfasserin |4 aut | |
| 700 | 1 | |a Michel, Angelika |e verfasserin |4 aut | |
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| 700 | 1 | |a Pawlita, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Schreiber, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Thomas F. |e verfasserin |4 aut | |
| 700 | 1 | |a Fingerle, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Tumani, Hayrettin |e verfasserin |4 aut | |
| 700 | 1 | |a Ehrenreich, Hannelore |e verfasserin |4 aut | |
| 700 | 1 | |a Kunzelmann, Karl |e verfasserin |4 aut | |
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10.2119/molmed.2014.00219 doi (DE-627)SPR008068607 (SPR)molmed.2014.00219-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.00 bkl Hammer, Christian verfasserin aut A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. Wanitchakool, Podchanart verfasserin aut Sirianant, Lalida verfasserin aut Papiol, Sergi verfasserin aut Monnheimer, Mathieu verfasserin aut Faria, Diana verfasserin aut Ousingsawat, Jiraporn verfasserin aut Schramek, Natalie verfasserin aut Schmitt, Corinna verfasserin aut Margos, Gabriele verfasserin aut Michel, Angelika verfasserin aut Kraiczy, Peter verfasserin aut Pawlita, Michael verfasserin aut Schreiber, Rainer verfasserin aut Schulz, Thomas F. verfasserin aut Fingerle, Volker verfasserin aut Tumani, Hayrettin verfasserin aut Ehrenreich, Hannelore verfasserin aut Kunzelmann, Karl verfasserin aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 21(2015), 1 vom: Jan., Seite 26-37 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:21 year:2015 number:1 month:01 pages:26-37 https://dx.doi.org/10.2119/molmed.2014.00219 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2014 GBV_ILN_2153 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 44.00 ASE AR 21 2015 1 01 26-37 |
| spelling |
10.2119/molmed.2014.00219 doi (DE-627)SPR008068607 (SPR)molmed.2014.00219-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.00 bkl Hammer, Christian verfasserin aut A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. Wanitchakool, Podchanart verfasserin aut Sirianant, Lalida verfasserin aut Papiol, Sergi verfasserin aut Monnheimer, Mathieu verfasserin aut Faria, Diana verfasserin aut Ousingsawat, Jiraporn verfasserin aut Schramek, Natalie verfasserin aut Schmitt, Corinna verfasserin aut Margos, Gabriele verfasserin aut Michel, Angelika verfasserin aut Kraiczy, Peter verfasserin aut Pawlita, Michael verfasserin aut Schreiber, Rainer verfasserin aut Schulz, Thomas F. verfasserin aut Fingerle, Volker verfasserin aut Tumani, Hayrettin verfasserin aut Ehrenreich, Hannelore verfasserin aut Kunzelmann, Karl verfasserin aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 21(2015), 1 vom: Jan., Seite 26-37 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:21 year:2015 number:1 month:01 pages:26-37 https://dx.doi.org/10.2119/molmed.2014.00219 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2014 GBV_ILN_2153 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 44.00 ASE AR 21 2015 1 01 26-37 |
| allfields_unstemmed |
10.2119/molmed.2014.00219 doi (DE-627)SPR008068607 (SPR)molmed.2014.00219-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.00 bkl Hammer, Christian verfasserin aut A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. Wanitchakool, Podchanart verfasserin aut Sirianant, Lalida verfasserin aut Papiol, Sergi verfasserin aut Monnheimer, Mathieu verfasserin aut Faria, Diana verfasserin aut Ousingsawat, Jiraporn verfasserin aut Schramek, Natalie verfasserin aut Schmitt, Corinna verfasserin aut Margos, Gabriele verfasserin aut Michel, Angelika verfasserin aut Kraiczy, Peter verfasserin aut Pawlita, Michael verfasserin aut Schreiber, Rainer verfasserin aut Schulz, Thomas F. verfasserin aut Fingerle, Volker verfasserin aut Tumani, Hayrettin verfasserin aut Ehrenreich, Hannelore verfasserin aut Kunzelmann, Karl verfasserin aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 21(2015), 1 vom: Jan., Seite 26-37 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:21 year:2015 number:1 month:01 pages:26-37 https://dx.doi.org/10.2119/molmed.2014.00219 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2014 GBV_ILN_2153 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 44.00 ASE AR 21 2015 1 01 26-37 |
| allfieldsGer |
10.2119/molmed.2014.00219 doi (DE-627)SPR008068607 (SPR)molmed.2014.00219-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.00 bkl Hammer, Christian verfasserin aut A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. Wanitchakool, Podchanart verfasserin aut Sirianant, Lalida verfasserin aut Papiol, Sergi verfasserin aut Monnheimer, Mathieu verfasserin aut Faria, Diana verfasserin aut Ousingsawat, Jiraporn verfasserin aut Schramek, Natalie verfasserin aut Schmitt, Corinna verfasserin aut Margos, Gabriele verfasserin aut Michel, Angelika verfasserin aut Kraiczy, Peter verfasserin aut Pawlita, Michael verfasserin aut Schreiber, Rainer verfasserin aut Schulz, Thomas F. verfasserin aut Fingerle, Volker verfasserin aut Tumani, Hayrettin verfasserin aut Ehrenreich, Hannelore verfasserin aut Kunzelmann, Karl verfasserin aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 21(2015), 1 vom: Jan., Seite 26-37 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:21 year:2015 number:1 month:01 pages:26-37 https://dx.doi.org/10.2119/molmed.2014.00219 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2014 GBV_ILN_2153 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 44.00 ASE AR 21 2015 1 01 26-37 |
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10.2119/molmed.2014.00219 doi (DE-627)SPR008068607 (SPR)molmed.2014.00219-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.00 bkl Hammer, Christian verfasserin aut A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. Wanitchakool, Podchanart verfasserin aut Sirianant, Lalida verfasserin aut Papiol, Sergi verfasserin aut Monnheimer, Mathieu verfasserin aut Faria, Diana verfasserin aut Ousingsawat, Jiraporn verfasserin aut Schramek, Natalie verfasserin aut Schmitt, Corinna verfasserin aut Margos, Gabriele verfasserin aut Michel, Angelika verfasserin aut Kraiczy, Peter verfasserin aut Pawlita, Michael verfasserin aut Schreiber, Rainer verfasserin aut Schulz, Thomas F. verfasserin aut Fingerle, Volker verfasserin aut Tumani, Hayrettin verfasserin aut Ehrenreich, Hannelore verfasserin aut Kunzelmann, Karl verfasserin aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 21(2015), 1 vom: Jan., Seite 26-37 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:21 year:2015 number:1 month:01 pages:26-37 https://dx.doi.org/10.2119/molmed.2014.00219 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2014 GBV_ILN_2153 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 44.00 ASE AR 21 2015 1 01 26-37 |
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coding variant of ano10, affecting volume regulation of macrophages, is associated with borrelia seropositivity |
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A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity |
| abstract |
Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. |
| abstractGer |
Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. |
| abstract_unstemmed |
Abstract In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding $ Cl^{−} $ channels and phospholipid scramblases. ANO10 augments volume-regulated $ Cl^{−} $ currents ($ I_{Hypo} $) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on $ I_{Hypo} $, RVD and intracellular $ Ca^{2+} $ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. |
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| title_short |
A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity |
| url |
https://dx.doi.org/10.2119/molmed.2014.00219 |
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Wanitchakool, Podchanart Sirianant, Lalida Papiol, Sergi Monnheimer, Mathieu Faria, Diana Ousingsawat, Jiraporn Schramek, Natalie Schmitt, Corinna Margos, Gabriele Michel, Angelika Kraiczy, Peter Pawlita, Michael Schreiber, Rainer Schulz, Thomas F. Fingerle, Volker Tumani, Hayrettin Ehrenreich, Hannelore Kunzelmann, Karl |
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Wanitchakool, Podchanart Sirianant, Lalida Papiol, Sergi Monnheimer, Mathieu Faria, Diana Ousingsawat, Jiraporn Schramek, Natalie Schmitt, Corinna Margos, Gabriele Michel, Angelika Kraiczy, Peter Pawlita, Michael Schreiber, Rainer Schulz, Thomas F. Fingerle, Volker Tumani, Hayrettin Ehrenreich, Hannelore Kunzelmann, Karl |
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| doi_str |
10.2119/molmed.2014.00219 |
| up_date |
2024-07-03T17:07:10.611Z |
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