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, 225 South ChongQing Road, Shanghai 200025, PR China.
Gene. 2013 Jan 10;512(2):300-4. doi: 10.1016/j.gene.2012.10.021. Epub 2012 Oct 27.
Graves' Disease (GD) is a common and complex disorder, with a strong hereditary component. IL-17F is a potent cytokine and a potential contributor to the etiology of various human autoimmune diseases. In the present study, we focused on the relationship between polymorphisms in the IL-17F gene and GD susceptibility through a case-control association study in two independent Chinese cohorts.
Our pilot study was performed on a cohort from Shanghai, which included 757 GD patients and 741 healthy controls. Our replication cohort was from Xiamen, consisting of 434 GD patients and 420 healthy controls. We selected four tag SNPs (rs763780, rs2397084, rs9463772 and rs761167) within the IL-17F gene to conduct a genotyping analysis.
In the Shanghai cohort, the rs9463772 polymorphism showed a significant association with GD and Graves' Disease-associated Ophthalmopathy (GO) patients (P(allele)=7×10(-5) and 7.4×10(-3) for GD and GO patients, respectively). The rs763780 polymorphism was found to have only a difference in genotype distribution between GD individuals and healthy controls (P=0.017). In the replication study, we confirmed the association between the rs9463772 polymorphism and GD susceptibility. Haplotype analysis showed that the haplotype of the four SNPs (GCTT) was associated with a significant risk of GD in the Shanghai cohort (P=7.9×10(-3)).
Our results suggest that polymorphisms in the IL-17F gene increase the risk of Graves' Disease and that IL-17F is therefore a good candidate gene for Graves' Disease prediction in the Han Chinese population.
格雷夫斯病（GD）是一种常见且复杂的疾病，具有很强的遗传成分。白细胞介素-17F（IL-17F）是一种有效的细胞因子，可能是各种人类自身免疫性疾病的病因之一。在本研究中，我们通过对两个独立的中国队列的病例对照关联研究，重点研究了 IL-17F 基因多态性与 GD 易感性之间的关系。
我们的初步研究是在上海的一个队列中进行的，该队列包括 757 名 GD 患者和 741 名健康对照者。我们的复制队列来自厦门，包括 434 名 GD 患者和 420 名健康对照者。我们选择了 IL-17F 基因内的四个标签 SNP（rs763780、rs2397084、rs9463772 和 rs761167）进行基因分型分析。
在上海队列中，rs9463772 多态性与 GD 和格雷夫斯眼病（GO）患者显著相关（GD 和 GO 患者的 P（等位基因）分别为 7×10（-5）和 7.4×10（-3））。rs763780 多态性仅在 GD 个体与健康对照组之间存在基因型分布差异（P=0.017）。在复制研究中，我们证实了 rs9463772 多态性与 GD 易感性之间的关联。单体型分析显示，上海队列中四个 SNP（GCTT）的单体型与 GD 的显著风险相关（P=7.9×10（-3））。
我们的结果表明，IL-17F 基因的多态性增加了 GD 的风险，因此 IL-17F 是汉族人群预测 GD 的一个候选基因。
