Confirmation of an association between rs6822844 at the IL2-IL21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus
AuthorMaiti, Amit K.
Tobön, Gabriel J.
Sawalha, Amr H.
Cherñavsky, Alejandra C.
Nath, Swapan K.
"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 (FST = 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 (Pmeta = 3.61 × 10-6), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (Pmeta = 3.48 × 10-12), type 1 DM (Pmeta = 5.33 × 10-5), and CD (Pmeta = 5.30 × 10-3). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; Pmeta = 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. © 2010, American College of Rheumatology."
Interleukin 2 ; systemic ; rheumatoid ; single nucleotide ; type 1 ; Interleukin 21 ; Allele ; Argentina ; Article ; Autoimmune disease ; Behcet disease ; Case control study ; Celiac disease ; Colombia ; Controlled study ; Data analysis ; Enteritis ; Europe ; Evaluation ; Evidence based medicine ; Genetic association ; Genetic susceptibility ; Human ; Insulin dependent diabetes mellitus ; Major clinical study ; Priority journal ; Rheumatoid arthritis ; Single nucleotide polymorphism ; Sjoegren syndrome ; Statistical significance ; Systemic lupus erythematosus ; Turkey (bird) ; Ulcerative colitis ; Argentina ; Arthritis ; Autoimmune diseases ; Case-control studies ; Colombia ; Diabetes mellitus ; Genetic predisposition to disease ; Genotype ; Humans ; Interleukin-2 ; Interleukins ; Lupus erythematosus ; Phenotype ; Polymorphism ; Sjogren's syndrome ; Turkey ;
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