Open AccessConfirmation of an association between rs6822844 at the Il2–Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus
Author(s) -
Maiti Amit K.,
KimHoward Xana,
Viswanathan Parvathi,
Guillén Laura,
RojasVillarraga Adriana,
Deshmukh Harshal,
Direskeneli Haner,
SaruhanDireskeneli Güher,
Cañas Carlos,
Tobön Gabriel J.,
Sawalha Amr H.,
Cherñavsky Alejandra C.,
Anaya JuanManuel,
Nath Swapan K.
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27222
Subject(s) - immunology , medicine , rheumatoid arthritis , inflammatory bowel disease , ulcerative colitis , autoimmune disease , population , allele , disease , genetics , biology , gene , environmental health
Objective Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2–IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune‐mediated diseases in non‐European populations, and to perform disease‐specific and overall meta‐analyses using data from previously published studies. Methods We evaluated case–control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta‐analyses were performed using data from the present study and previous studies. Results We detected significant associations of rs6822844 with SLE ( P = 0.008), type 1 DM ( P = 0.014), RA ( P = 0.019), and primary SS ( P = 0.033) but not with BD ( P = 0.34) or CD ( P = 0.98). We identified little evidence of population differentiation ( F ST = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease‐specific meta‐analysis indicated significant association for RA ( P meta = 3.61 × 10 −6 ), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) ( P meta = 3.48 × 10 −12 ), type 1 DM ( P meta = 5.33 × 10 −5 ), and CD ( P meta = 5.30 × 10 −3 ). Overall meta‐analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; P meta = 2.61 × 10 −25 , odds ratio 0.73 [95% confidence interval 0.69–0.78]). Conclusion Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non‐European populations. Meta‐analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European‐derived and non‐European populations.