Confirmation of an association between rs6822844 at the Il2–Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus

✍ Scribed by Amit K. Maiti; Xana Kim-Howard; Parvathi Viswanathan; Laura Guillén; Adriana Rojas-Villarraga; Harshal Deshmukh; Haner Direskeneli; Güher Saruhan-Direskeneli; Carlos Cañas; Gabriel J. Tobön; Amr H. Sawalha; Alejandra C. Cherñavsky; Juan-Manuel Anaya; Swapan K. Nath

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 88 KB
• Volume: 62
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.27222

✦ Synopsis

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 Sjo ¨gren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behc ¸et'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. Metaanalysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.

Genetic susceptibility plays an important role in autoimmune diseases. Many susceptibility genes/loci