Association study of interleukin-12A gene polymorphisms with Graves' disease in two Chinese populations

Objective Graves' disease (GD) is a common autoimmune disorder and genetic and environmental factors contributing to its aetiology. The pro-inflammatory cytokine interleukin-12 (IL-12) is believed to be critically involved in the pathogenesis of GD. This study aims to elucidate the effect of IL-12A gene polymorphisms on GD. Design and methods A case-control association study of five tag single nucleotide polymorphisms (SNPs) (rs2243115, rs2243123, rs583911, rs568408 and rs2243143) within the IL-12A gene was performed in two independent Chinese cohorts. A pilot cohort conducted in Shanghai consisted of 701 patients and 686 controls and a replicate cohort in Xiamen Island included 378 patients and 312 controls. The five SNPs were genotyped by the SNPstream Genotyping Systems and Taqman PCR method. Results Polymorphism of rs568408, located at the 3'-UTRregion, was found to have a significant association with GD in both the cohorts (P-allele = 2.96 x 10(-7) and Pallele = 0 013 for Shanghai and Xiamen Island cohorts, respectively). Haplotype analysis showed that the haplotype of the five SNPs (TTAAG) was associated with a significant risk of GD in both the cohorts (OR = 2.04 and OR = 1.70 for Shanghai and Xiamen Island cohorts, respectively). Conclusion Our results have established an association between IL-12A polymorphism and GD susceptibility in the Chinese population.