Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study. Kirsten, H., Petit-Teixeira, E., Scholz, M., Hasenclever, D., Hantmann, H., Heider, D., Wagner, U., Sack, U., Hugo Teixeira, V., Prum, B., Burkhardt, J., Pierlot, C., Emmrich, F., Cornelis, F., & Ahnert, P. Arthritis research \& therapy, 11(3):R60, 2009. abstract bibtex INTRODUCTION̊\nThe gene MICA encodes the protein major histocompatibility complex class I polypeptide-related sequence A. It is expressed in synovium of patients with rheumatoid arthritis (RA) and its implication in autoimmunity is discussed. We analyzed the association of genetic variants of MICA with susceptibility to RA.̊\nMETHODS̊\nInitially, 300 French Caucasian individuals belonging to 100 RA trio families were studied. An additional 100 independent RA trio families and a German Caucasian case-control cohort (90/182 individuals) were available for replication. As MICA is situated in proximity to known risk alleles of the HLA-DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with transmission disequilibrium test (TDT) or by implementing a regression model including all available data. Analysis included a microsatellite polymorphism (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.̊\nRESULTS̊\nIn contrast to the other investigated polymorphisms, the non-synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the replication family sample showed only a trend, combined family data remained consistent with the hypothesis of MICA-250 association independent from shared epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to 0.83, P = 0.003). We also replicated the protective association of MICA-250A within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005; regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete linkage disequilibrium of MICA-250 (D' = 1, r2= 1) with the functional MICA variant rs1051792 (D' = 1, r2= 1). As rs1051792 confers differential allelic affinity of MICA to the receptor NKG2D, this provides a possible functional explanation for the observed association.̊\nCONCLUSIONS̊\nWe present evidence for linkage and association of MICA-250 (rs1051794) with RA independent of known HLA-DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more studies within other populations are necessary to prove the general relevance of this polymorphism for RA.
@article{ Kirsten.2009c,
abstract = {INTRODUCTION̊\nThe gene MICA encodes the protein major histocompatibility complex class I polypeptide-related sequence A. It is expressed in synovium of patients with rheumatoid arthritis (RA) and its implication in autoimmunity is discussed. We analyzed the association of genetic variants of MICA with susceptibility to RA.̊\nMETHODS̊\nInitially, 300 French Caucasian individuals belonging to 100 RA trio families were studied. An additional 100 independent RA trio families and a German Caucasian case-control cohort (90/182 individuals) were available for replication. As MICA is situated in proximity to known risk alleles of the HLA-DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with transmission disequilibrium test (TDT) or by implementing a regression model including all available data. Analysis included a microsatellite polymorphism (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.̊\nRESULTS̊\nIn contrast to the other investigated polymorphisms, the non-synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the replication family sample showed only a trend, combined family data remained consistent with the hypothesis of MICA-250 association independent from shared epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to 0.83, P = 0.003). We also replicated the protective association of MICA-250A within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005; regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete linkage disequilibrium of MICA-250 (D' = 1, r2= 1) with the functional MICA variant rs1051792 (D' = 1, r2= 1). As rs1051792 confers differential allelic affinity of MICA to the receptor NKG2D, this provides a possible functional explanation for the observed association.̊\nCONCLUSIONS̊\nWe present evidence for linkage and association of MICA-250 (rs1051794) with RA independent of known HLA-DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more studies within other populations are necessary to prove the general relevance of this polymorphism for RA.},
added-at = {2014-10-15T15:04:05.000+0200},
author = {Kirsten, Holger and Petit-Teixeira, Elisabeth and Scholz, Markus and Hasenclever, Dirk and Hantmann, Helene and Heider, Dirk and Wagner, Ulf and Sack, Ulrich and {Hugo Teixeira}, Vitor and Prum, Bernard and Burkhardt, Jana and Pierlot, Céline and Emmrich, Frank and Cornelis, François and Ahnert, Peter},
biburl = {http://www.bibsonomy.org/bibtex/2595034216ffaa5748f97ae20ad6003c3/drtester},
interhash = {3b1a53bc6c7630c981549bfa42ae881d},
intrahash = {595034216ffaa5748f97ae20ad6003c3},
journal = {Arthritis research \& therapy},
keywords = {Adult Alleles Arthritis,_Rheumatoid/genetics/immunology Case-Control_Studies Cohort_Studies Family Female Genetic_Linkage/immunology Genetic_Predisposition_to_Disease/genetics Genetic_Variation/immunology HLA-DR_Antigens/genetics HLA-DRB1_Chains Histocompatibility_Antigens_Class_I/genetics Humans Male Middle_Aged Polymorphism,_Single_Nucleotide/genetics Risk_Factors},
number = {3},
pages = {R60},
title = {Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study},
volume = {11},
year = {2009}
}
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{"_id":"earD2WjoPp57KwzdQ","bibbaseid":"kirsten-petitteixeira-scholz-hasenclever-hantmann-heider-wagner-sack-hugoteixeira-prum-burkhardt-pierlot-emmrich-cornelis-ahnert-associationofmicawithrheumatoidarthritisindependentofknownhladrb1riskallelesinafamilybasedandacasecontrolstudy-2009","downloads":0,"creationDate":"2015-05-07T12:05:12.573Z","title":"Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study","author_short":["Kirsten, H.","Petit-Teixeira, E.","Scholz, M.","Hasenclever, D.","Hantmann, H.","Heider, D.","Wagner, U.","Sack, U.","Hugo Teixeira, V.","Prum, B.","Burkhardt, J.","Pierlot, C.","Emmrich, F.","Cornelis, F.","Ahnert, P."],"year":2009,"bibtype":"article","biburl":"http://www.bibsonomy.org/bib/author/bernard?items=1000","bibdata":{"abstract":"INTRODUCTION̊\\nThe gene MICA encodes the protein major histocompatibility complex class I polypeptide-related sequence A. It is expressed in synovium of patients with rheumatoid arthritis (RA) and its implication in autoimmunity is discussed. We analyzed the association of genetic variants of MICA with susceptibility to RA.̊\\nMETHODS̊\\nInitially, 300 French Caucasian individuals belonging to 100 RA trio families were studied. An additional 100 independent RA trio families and a German Caucasian case-control cohort (90/182 individuals) were available for replication. As MICA is situated in proximity to known risk alleles of the HLA-DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with transmission disequilibrium test (TDT) or by implementing a regression model including all available data. Analysis included a microsatellite polymorphism (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.̊\\nRESULTS̊\\nIn contrast to the other investigated polymorphisms, the non-synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the replication family sample showed only a trend, combined family data remained consistent with the hypothesis of MICA-250 association independent from shared epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to 0.83, P = 0.003). We also replicated the protective association of MICA-250A within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005; regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete linkage disequilibrium of MICA-250 (D' = 1, r2= 1) with the functional MICA variant rs1051792 (D' = 1, r2= 1). As rs1051792 confers differential allelic affinity of MICA to the receptor NKG2D, this provides a possible functional explanation for the observed association.̊\\nCONCLUSIONS̊\\nWe present evidence for linkage and association of MICA-250 (rs1051794) with RA independent of known HLA-DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more studies within other populations are necessary to prove the general relevance of this polymorphism for RA.","added-at":"2014-10-15T15:04:05.000+0200","author":["Kirsten, Holger","Petit-Teixeira, Elisabeth","Scholz, Markus","Hasenclever, Dirk","Hantmann, Helene","Heider, Dirk","Wagner, Ulf","Sack, Ulrich","Hugo Teixeira, Vitor","Prum, Bernard","Burkhardt, Jana","Pierlot, Céline","Emmrich, Frank","Cornelis, François","Ahnert, Peter"],"author_short":["Kirsten, H.","Petit-Teixeira, E.","Scholz, M.","Hasenclever, D.","Hantmann, H.","Heider, D.","Wagner, U.","Sack, U.","Hugo Teixeira, V.","Prum, B.","Burkhardt, J.","Pierlot, C.","Emmrich, F.","Cornelis, F.","Ahnert, P."],"bibtex":"@article{ Kirsten.2009c,\n abstract = {INTRODUCTION̊\\nThe gene MICA encodes the protein major histocompatibility complex class I polypeptide-related sequence A. It is expressed in synovium of patients with rheumatoid arthritis (RA) and its implication in autoimmunity is discussed. We analyzed the association of genetic variants of MICA with susceptibility to RA.̊\\nMETHODS̊\\nInitially, 300 French Caucasian individuals belonging to 100 RA trio families were studied. An additional 100 independent RA trio families and a German Caucasian case-control cohort (90/182 individuals) were available for replication. As MICA is situated in proximity to known risk alleles of the HLA-DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with transmission disequilibrium test (TDT) or by implementing a regression model including all available data. Analysis included a microsatellite polymorphism (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.̊\\nRESULTS̊\\nIn contrast to the other investigated polymorphisms, the non-synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the replication family sample showed only a trend, combined family data remained consistent with the hypothesis of MICA-250 association independent from shared epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to 0.83, P = 0.003). We also replicated the protective association of MICA-250A within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005; regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete linkage disequilibrium of MICA-250 (D' = 1, r2= 1) with the functional MICA variant rs1051792 (D' = 1, r2= 1). As rs1051792 confers differential allelic affinity of MICA to the receptor NKG2D, this provides a possible functional explanation for the observed association.̊\\nCONCLUSIONS̊\\nWe present evidence for linkage and association of MICA-250 (rs1051794) with RA independent of known HLA-DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more studies within other populations are necessary to prove the general relevance of this polymorphism for RA.},\n added-at = {2014-10-15T15:04:05.000+0200},\n author = {Kirsten, Holger and Petit-Teixeira, Elisabeth and Scholz, Markus and Hasenclever, Dirk and Hantmann, Helene and Heider, Dirk and Wagner, Ulf and Sack, Ulrich and {Hugo Teixeira}, Vitor and Prum, Bernard and Burkhardt, Jana and Pierlot, Céline and Emmrich, Frank and Cornelis, François and Ahnert, Peter},\n biburl = {http://www.bibsonomy.org/bibtex/2595034216ffaa5748f97ae20ad6003c3/drtester},\n interhash = {3b1a53bc6c7630c981549bfa42ae881d},\n intrahash = {595034216ffaa5748f97ae20ad6003c3},\n journal = {Arthritis research \\& therapy},\n keywords = {Adult Alleles Arthritis,_Rheumatoid/genetics/immunology Case-Control_Studies Cohort_Studies Family Female Genetic_Linkage/immunology Genetic_Predisposition_to_Disease/genetics Genetic_Variation/immunology HLA-DR_Antigens/genetics HLA-DRB1_Chains Histocompatibility_Antigens_Class_I/genetics Humans Male Middle_Aged Polymorphism,_Single_Nucleotide/genetics Risk_Factors},\n number = {3},\n pages = {R60},\n title = {Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study},\n volume = {11},\n year = {2009}\n}","bibtype":"article","biburl":"http://www.bibsonomy.org/bibtex/2595034216ffaa5748f97ae20ad6003c3/drtester","id":"Kirsten.2009c","interhash":"3b1a53bc6c7630c981549bfa42ae881d","intrahash":"595034216ffaa5748f97ae20ad6003c3","journal":"Arthritis research \\& therapy","key":"Kirsten.2009c","keywords":"Adult Alleles Arthritis,_Rheumatoid/genetics/immunology Case-Control_Studies Cohort_Studies Family Female Genetic_Linkage/immunology Genetic_Predisposition_to_Disease/genetics Genetic_Variation/immunology HLA-DR_Antigens/genetics HLA-DRB1_Chains Histocompatibility_Antigens_Class_I/genetics Humans Male Middle_Aged Polymorphism,_Single_Nucleotide/genetics Risk_Factors","number":"3","pages":"R60","title":"Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study","type":"article","volume":"11","year":"2009","bibbaseid":"kirsten-petitteixeira-scholz-hasenclever-hantmann-heider-wagner-sack-hugoteixeira-prum-burkhardt-pierlot-emmrich-cornelis-ahnert-associationofmicawithrheumatoidarthritisindependentofknownhladrb1riskallelesinafamilybasedandacasecontrolstudy-2009","role":"author","urls":{},"keyword":["Adult Alleles Arthritis","_Rheumatoid/genetics/immunology Case-Control_Studies Cohort_Studies Family Female Genetic_Linkage/immunology Genetic_Predisposition_to_Disease/genetics Genetic_Variation/immunology HLA-DR_Antigens/genetics HLA-DRB1_Chains Histocompatibility_Antigens_Class_I/genetics Humans Male Middle_Aged Polymorphism","_Single_Nucleotide/genetics Risk_Factors"],"downloads":0},"search_terms":["association","mica","rheumatoid","arthritis","independent","known","hla","drb1","risk","alleles","family","based","case","control","study","kirsten","petit-teixeira","scholz","hasenclever","hantmann","heider","wagner","sack","hugo teixeira","prum","burkhardt","pierlot","emmrich","cornelis","ahnert"],"keywords":["adult alleles arthritis","_rheumatoid/genetics/immunology case-control_studies cohort_studies family female genetic_linkage/immunology genetic_predisposition_to_disease/genetics genetic_variation/immunology hla-dr_antigens/genetics hla-drb1_chains histocompatibility_antigens_class_i/genetics humans male middle_aged polymorphism","_single_nucleotide/genetics risk_factors"],"authorIDs":[],"dataSources":["wvAhRjakvxMweG8ZA"]}