Genetic association between Interleukin-17A gene polymorphisms and the pathogenesis of Graves' disease in the Han Chinese population

Yicheng Qi; Huan Zheng; Nan Liu; Ting Guo; Wei Zhu; Shu Wang; Bin Cui; Guang Ning

doi:10.1111/cen.12725

Genetic association between Interleukin-17A gene polymorphisms and the pathogenesis of Graves' disease in the Han Chinese population

Clin Endocrinol (Oxf). 2016 Feb;84(2):265-270. doi: 10.1111/cen.12725. Epub 2015 Feb 24.

Authors

Yicheng Qi¹, Huan Zheng², Nan Liu¹, Ting Guo³, Wei Zhu¹, Shu Wang¹, Bin Cui^{1

3}, Guang Ning^{1

3}

Affiliations

¹ Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
² Geriatrics Department, Tongji Hospital Affiliated to Tongji University, Shanghai, China.
³ Laboratory Endocrine & Metabolic Diseases of Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China.

PMID: 25597472
DOI: 10.1111/cen.12725

Abstract

Objective: Graves' disease, one of the commonest autoimmune disorders, has a complex genetic basis. Interleukin-17A (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 Graves' disease (GD).

Design and methods: Our pilot study was performed on a cohort from Shanghai, which included 713 patients with GD and 756 healthy controls. A replicate cohort was from Xiamen, recruiting 444 patients with GD and 427 healthy subjects. Six single nucleotide polymorphisms (SNPs) (rs4711998, rs3819024, rs2275913, rs8193037, rs3819025 and rs3748067) within the IL-17A gene were genotyped by the SNPstream Genotyping Systems and Taqman PCR method.

Results: In Shanghai cohorts, the frequencies of rs8193037 alleles were strongly different between patients with Graves' 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 Graves' 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 Graves' disease than in controls [Graves' 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 Graves' disease-associated ophthalmopathy patients and controls in Shanghai cohorts. Haplotype association analysis also identified five main haplotypes of those six SNPs.

Conclusion: These results suggested that the polymorphism of IL-17A rs8193037 was strongly associated with Graves' disease susceptibility in the Chinese Han population.z.