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Numerous Autoimmune Diseases Associated with rs6822844 at the Il2-Il21 Region

Celiac.com 02/26/2010 - Data increasingly supports an association between rs6822844 at the IL2-IL21 region and multiple autoimmune diseases in individuals of European descent. A number of autoimmune diseases share susceptibility genes, pointing to similar molecular mechanisms.

A team of researchers recently set out to assess evidence for a general susceptibility locus by looking for association between rs6822844 at the Il2-Il21 region and numerous autoimmune diseases.

The research team included 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, and Swapan K. Nath

Their joint effort was underwritten by grants from the National Institutes of Health (NIH - Grant Number: 5R01-AI-063622, P20-RR-020143), Colciencias (Grant Number: 2213-04-16484), Rosario University School of Medicine, and the Colombian Association of Rheumatology.

The goal of the study was to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to conduct disease-specific and overall meta-analyses using data from previously published studies.

The team evaluated case-control associations between rs6822844 and celiac disease in subjects from Argentina; rheumatoid arthritis, type 1 diabetes mellitus, primary Sjögren's syndrome, and systemic lupus erythematosus in subjects from Colombia; and Behçet's disease in subjects from Turkey.

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They compared allele and gene distribution between cases and controls. They conducted meta-analyses using data from the present study and previous studies.

The team found significant associations of rs6822844 with systemic lupus erythematosus (P = 0.008), type 1 diabetes mellitus (P = 0.014), rheumatoid arthritis (P = 0.019), and primary Sjögren's syndrome (P = 0.033) but not with Behçet's disease (P = 0.34) or celiac disease (P = 0.98).

Cases and controls from Argentina and Colombia showed little evidence of population differentiation (FST = 0.01), which suggests that association was not influenced by population substructure.

Disease-specific meta-analysis shows strong association for rheumatoid arthritis (Pmeta = 3.61 × 10-6), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (Pmeta = 3.48 × 10-12), type 1 diabetes mellitus (Pmeta = 5.33 × 10-5), and celiac disease (Pmeta = 5.30 × 10-3).

Total meta-analysis across all autoimmune diseases supports association with rs6822844 (23 data sets; Pmeta = 2.61 × 10-25, odds ratio 0.73, with 95% confidence interval 0.69-0.78).

The team concludes that an association exists between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis provides strong confirmation for strong association across multiple autoimmune diseases in populations of both European and non-European ancestry.

Arthritis & Rheumatism; Volume 62 Issue 2, Pages 323 - 329


http://www3.interscience.wiley.com/journal/123266977/abstract?CRETRY=1&SRETRY=0

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