TNFSF15 Polymorphisms are Associated with Graves' Disease and Graves' Ophthalmopathy in a Han Chinese Population

Previous studies revealed an association of tumor necrosis factor super family-15 (TNFSF15) gene polymorphisms with several autoimmune diseases, but their roles in the development of Graves' disease (GD) and Graves' ophthalmopathy (GO) remain unclear. The aim of this study was to explore the correlation between TNFSF15 single nucleotide polymorphisms (SNPs) and susceptibility to GD and GO in a Han Chinese population.

This case-control study enrolled 813 healthy controls and 315 GD patients including 229 patients with GO. Eight SNPs of TNFSF15 (rs3810936, rs6478108, rs6478106, rs4979462, rs10817669, rs4246905, rs10733612, and rs10759734) were detected by TaqMan real-time PCR assay or PCR-restriction fragment length polymorphism (PCR-RFLP) and the possible association of these eight SNPs with the risk of GD and GO was analyzed. Allele frequencies and genotype distributions were compared using χ² test. A stratified analysis was also performed according to clinical activity score (CAS) and sex.

In comparison with the controls, the CT genotype of rs3810936 and the T allele of rs4979462 were decreased in GD patients. GD patients with GO also showed a lower frequency of the rs3810936 CT genotype and the rs4979462 T allele than the controls. Inactive GO patients showed a lower frequency of the rs3810936 CT genotype than controls, while GD females demonstrated a lower incidence of the T allele in rs4979462 and rs6478106 than the controls. Furthermore, GO females exhibited a lower rate of the rs4979462 T allele than the controls.

Our results suggest that TNFSF15 rs3810936 and rs4979462 polymorphisms are associated with the susceptibility of GD and GO in a Han Chinese population. Additionally, rs3810936 may affect the activity of GO, and rs4979462 may correlate with the sexual dimorphism observed in GD and GO.