Genetic association between Interleukin‐17A gene polymorphisms and the pathogenesis of G raves’ disease in the H an C hinese population

Summary Objective Graves’ disease, one of the commonest autoimmune disorders, has a complex genetic basis. Interleukin‐17 A ( IL ‐17A) is an important cytokine involved in innate and adaptive immune responses. This case–control study sought to investigate genetic association between the IL‐17A gene and the process of G raves’ disease ( GD ). Design and methods Our pilot study was performed on a cohort from S hanghai, which included 713 patients with GD and 756 healthy controls. A replicate cohort was from X iamen, recruiting 444 patients with GD and 427 healthy subjects. Six single nucleotide polymorphisms ( SNP s) (rs4711998, rs3819024, rs2275913, rs8193037, rs3819025 and rs3748067) within the IL‐17A gene were genotyped by the SNP stream G enotyping S ystems and T aqman PCR method. Results In S hanghai cohorts, the frequencies of rs8193037 alleles were strongly different between patients with G raves’ disease ( G , 87·6% and A , 12·4%) and healthy controls ( G , 91·4% and A , 8·6%) ( P  =   0·00067). The A carriers were associated with increased G raves’ disease risks when compared with the G carriers ( OR  = 1·51, 95% CI  = 1·19‐1·92). In replicate cohorts, the proportion of individuals carrying the A allele of rs8193037 was significantly higher in patients with G raves’ disease than in controls [ G raves’ disease vs control, 14·3% vs 9·1%, OR  = 1·66 (95% CI : 1·23–2·24), P allele  = 0·0082]. In addition, rs8193037 and rs3748067 were found to be different in both genotype and allele distributions in G raves’ disease‐associated ophthalmopathy patients and controls in S hanghai cohorts. Haplotype association analysis also identified five main haplotypes of those six SNP s. Conclusion These results suggested that the polymorphism of IL ‐17A rs8193037 was strongly associated with G raves’ disease susceptibility in the C hinese H an population.z