Dense mapping of IL2 RA shows no association with Graves' disease in Chinese Han population.

Objective Associations between IL2 RA and various autoimmune diseases have been reported in Caucasians. We investigated whether genetic polymorphisms at the IL2 RA locus were associated with Graves' disease ( GD) in the Chinese Han population. Design We performed a genome-wide association study ( GWAS) in 1 536 GD patients and 1 516 controls. The 1000 Genomes Project data were adopted as references for imputation analysis. After forward and conditional logistic regressions, we found that rs11256313 was the major risk variant in the CD25/ IL2 RA region. Thus, we further genotyped rs11256313 in a replication cohort with 3 694 GD patients and 3 510 controls using ABI 7900 HT TaqMan Real-Time PCR System. Results Nine single nucleotide polymorphisms ( SNPs) in the IL2 RA block were nominally associated with GD in our GWAS (0·01 < P < 0·05). After imputation analysis, 13 imputed SNPs in the IL2 RA block were weakly associated with GD ( P ≤ 0·05). Logistic regression analysis suggested that the imputed rs11256313 could represent the IL2 RA block ( P = 0·003). However, we failed to replicate the association of rs11256313 in a larger cohort ( P = 0·145). A subphenotype analysis of rs11256313 on thyroid hormone receptor antibody ( TRAb) and gender showed that there was no association in any of the subphenotype groups ( P > 0·05). Conclusions The results suggested that common genetic polymorphisms at IL2 RA do not exert a significant genetic effect on the development of GD in the Chinese Han population. Previously reported associations between CD25/ IL2 RA and autoimmune diseases including GD in Caucasians again imply that heterogeneity exists in different ethnic populations. [ABSTRACT FROM AUTHOR]