Genetic association between Interleukin-17A gene polymorphisms and the pathogenesis of Graves' disease in the Han Chinese population
Genetic association between Interleukin-17A gene polymorphisms and the pathogenesis of Graves' disease in the Han Chinese population
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DOI：
10.1111/cen.12725
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发表时间：
2016-02-01
影响因子：
3.2
通讯作者：
Ning, Guang
中科院分区：
文献类型：
--
作者：
Qi, Yicheng;Zheng, Huan;Ning, Guang
目的 格雷夫斯病是最常见的自身免疫性疾病之一，具有复杂的遗传基础。白介素-17A (IL-17A) 是一种重要的细胞因子，参与先天性和适应性免疫反应。这项病例对照研究旨在调查 IL-17A 基因与格雷夫斯病 (GD) 过程之间的遗传关联。设计和方法我们的初步研究是在上海的队列中进行的，其中包括 713 名 GD 患者和 756 名健康对照者。重复队列来自厦门，招募了 444 名 GD 患者和 427 名健康受试者。采用SNPstream基因分型系统和Taqman PCR方法对IL-17A基因内的6个单核苷酸多态性（SNP）（rs4711998、rs3819024、rs2275913、rs8193037、rs3819025和rs3748067）进行基因分型。 在队列中，rs8193037 等位基因的频率在 Graves 病患者（G，87.6% 和 A，12.4%）和健康对照（G，91.4% 和 A，8.6%）之间存在显着差异（P = 0.00067）。与 G 携带者相比，A 携带者与格雷夫斯病风险增加相关（OR = 1.51，95% CI = 1.19-1.92）。在重复队列中，格雷夫斯病患者中携带 rs8193037 A 等位基因的个体比例显着高于对照组 [格雷夫斯病与对照，14.3% vs 9.1%，OR = 1.66 (95% CI: 1.23-2.24)，Pallele = 0.0082]。此外，在上海队列的格雷夫斯病相关眼病患者和对照中，发现rs8193037和rs3748067的基因型和等位基因分布存在差异。单倍型关联分析还鉴定了这 6 个 SNP 的 5 个主要单倍型。结论这些结果表明 IL-17A rs8193037 多态性与中国汉族人群 Graves 病易感性密切相关。
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), Pallele = 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