<it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis
<p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group...
Ausführliche Beschreibung
Autor*in: |
Owusu-Dabo Ellis [verfasserIn] Förster Birgit [verfasserIn] Thye Thorsten [verfasserIn] Intemann Christopher D [verfasserIn] Gyapong John [verfasserIn] Horstmann Rolf D [verfasserIn] Meyer Christian G [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2011 |
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Übergeordnetes Werk: |
In: BMC Genetics - BMC, 2003, 12(2011), 1, p 34 |
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Übergeordnetes Werk: |
volume:12 ; year:2011 ; number:1, p 34 |
Links: |
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DOI / URN: |
10.1186/1471-2156-12-34 |
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Katalog-ID: |
DOAJ020946910 |
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520 | |a <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< | ||
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10.1186/1471-2156-12-34 doi (DE-627)DOAJ020946910 (DE-599)DOAJd32ad255283446fb8ace63749fc6fda6 DE-627 ger DE-627 rakwb eng QH426-470 Owusu-Dabo Ellis verfasserin aut <it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< Genetics Förster Birgit verfasserin aut Thye Thorsten verfasserin aut Intemann Christopher D verfasserin aut Gyapong John verfasserin aut Horstmann Rolf D verfasserin aut Meyer Christian G verfasserin aut In BMC Genetics BMC, 2003 12(2011), 1, p 34 (DE-627)326644938 (DE-600)2041497-3 14712156 nnns volume:12 year:2011 number:1, p 34 https://doi.org/10.1186/1471-2156-12-34 kostenfrei https://doaj.org/article/d32ad255283446fb8ace63749fc6fda6 kostenfrei http://www.biomedcentral.com/1471-2156/12/34 kostenfrei https://doaj.org/toc/1471-2156 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 12 2011 1, p 34 |
spelling |
10.1186/1471-2156-12-34 doi (DE-627)DOAJ020946910 (DE-599)DOAJd32ad255283446fb8ace63749fc6fda6 DE-627 ger DE-627 rakwb eng QH426-470 Owusu-Dabo Ellis verfasserin aut <it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< Genetics Förster Birgit verfasserin aut Thye Thorsten verfasserin aut Intemann Christopher D verfasserin aut Gyapong John verfasserin aut Horstmann Rolf D verfasserin aut Meyer Christian G verfasserin aut In BMC Genetics BMC, 2003 12(2011), 1, p 34 (DE-627)326644938 (DE-600)2041497-3 14712156 nnns volume:12 year:2011 number:1, p 34 https://doi.org/10.1186/1471-2156-12-34 kostenfrei https://doaj.org/article/d32ad255283446fb8ace63749fc6fda6 kostenfrei http://www.biomedcentral.com/1471-2156/12/34 kostenfrei https://doaj.org/toc/1471-2156 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 12 2011 1, p 34 |
allfields_unstemmed |
10.1186/1471-2156-12-34 doi (DE-627)DOAJ020946910 (DE-599)DOAJd32ad255283446fb8ace63749fc6fda6 DE-627 ger DE-627 rakwb eng QH426-470 Owusu-Dabo Ellis verfasserin aut <it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< Genetics Förster Birgit verfasserin aut Thye Thorsten verfasserin aut Intemann Christopher D verfasserin aut Gyapong John verfasserin aut Horstmann Rolf D verfasserin aut Meyer Christian G verfasserin aut In BMC Genetics BMC, 2003 12(2011), 1, p 34 (DE-627)326644938 (DE-600)2041497-3 14712156 nnns volume:12 year:2011 number:1, p 34 https://doi.org/10.1186/1471-2156-12-34 kostenfrei https://doaj.org/article/d32ad255283446fb8ace63749fc6fda6 kostenfrei http://www.biomedcentral.com/1471-2156/12/34 kostenfrei https://doaj.org/toc/1471-2156 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 12 2011 1, p 34 |
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10.1186/1471-2156-12-34 doi (DE-627)DOAJ020946910 (DE-599)DOAJd32ad255283446fb8ace63749fc6fda6 DE-627 ger DE-627 rakwb eng QH426-470 Owusu-Dabo Ellis verfasserin aut <it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< Genetics Förster Birgit verfasserin aut Thye Thorsten verfasserin aut Intemann Christopher D verfasserin aut Gyapong John verfasserin aut Horstmann Rolf D verfasserin aut Meyer Christian G verfasserin aut In BMC Genetics BMC, 2003 12(2011), 1, p 34 (DE-627)326644938 (DE-600)2041497-3 14712156 nnns volume:12 year:2011 number:1, p 34 https://doi.org/10.1186/1471-2156-12-34 kostenfrei https://doaj.org/article/d32ad255283446fb8ace63749fc6fda6 kostenfrei http://www.biomedcentral.com/1471-2156/12/34 kostenfrei https://doaj.org/toc/1471-2156 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 12 2011 1, p 34 |
allfieldsSound |
10.1186/1471-2156-12-34 doi (DE-627)DOAJ020946910 (DE-599)DOAJd32ad255283446fb8ace63749fc6fda6 DE-627 ger DE-627 rakwb eng QH426-470 Owusu-Dabo Ellis verfasserin aut <it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< Genetics Förster Birgit verfasserin aut Thye Thorsten verfasserin aut Intemann Christopher D verfasserin aut Gyapong John verfasserin aut Horstmann Rolf D verfasserin aut Meyer Christian G verfasserin aut In BMC Genetics BMC, 2003 12(2011), 1, p 34 (DE-627)326644938 (DE-600)2041497-3 14712156 nnns volume:12 year:2011 number:1, p 34 https://doi.org/10.1186/1471-2156-12-34 kostenfrei https://doaj.org/article/d32ad255283446fb8ace63749fc6fda6 kostenfrei http://www.biomedcentral.com/1471-2156/12/34 kostenfrei https://doaj.org/toc/1471-2156 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 12 2011 1, p 34 |
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Owusu-Dabo Ellis @@aut@@ Förster Birgit @@aut@@ Thye Thorsten @@aut@@ Intemann Christopher D @@aut@@ Gyapong John @@aut@@ Horstmann Rolf D @@aut@@ Meyer Christian G @@aut@@ |
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<it<MCP1 </it<haplotypes associated with protection from pulmonary tuberculosis |
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<p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< |
abstractGer |
<p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< |
abstract_unstemmed |
<p<Abstract</p< <p<Background</p< <p<The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the <it<MCP1 </it<-362C and the <it<MCP1 </it<-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the <it<MCP1 </it<gene in order to determine causal variants or haplotypes genetically and functionally.</p< <p<Results</p< <p<A 14 base-pair deletion in the first <it<MCP1 </it<intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, P<sub<corrected </sub<= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, P<sub<nominal </sub<= 0.00002; adjusted P<sub<global </sub<= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the <it<MCP1 </it<mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.</p< <p<Conclusions</p< <p<In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the <it<MCP1 </it<-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.</p< |
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