Genetic association between IL-17F gene polymorphisms and the pathogenesis of Graves' Disease in the Han Chinese population

Abstract

Background: 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. Methods: 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. Results: In the Shanghai cohort, the rs9463772 polymorphism showed a significant association with GD and Graves' Disease-associated Ophthalmopathy (GO) patients (Pallele=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). Conclusion: 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. © 2012 Elsevier B.V.