TNFSF15 Polymorphisms Are Associated With Graves’ Ophthalmopathy In A Han Chinese Population

Background:Graves’ophthalmopathy(GO),also called thyroid associated ophthalmopathy(TAO),is considered to be a kind of autoimmune disease which was mediated by T cell and closely related to genetic factors.Recent studies have indicated that the TNFSF15 gene,which encodes TL1A protein,belonging to a member of the TNF family,can have a regulation of T cells’activation and differentiation,exerting a vital role in immune-regulation and development of inflammatory disease.Previous studies revealed an association of TNFSF15 single nucleotide polymorphisms(SNPs)with several autoimmune diseases,but their roles in the development of GO remain unclear.Therefore,the aim of our study was to explore the correlation between TNFSF15 SNPs and their susceptibility to GO in a Han Chinese population.Methods:This case-control study enrolled 813 healthy controls and315 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-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 usingχ~2 test.A stratified analysis was also performed according to clinical activity score(CAS)and sex.Results:In comparison with the controls,the CT genotype of rs3810936 and the T allele of rs4979462 were decreased in GD patients(P=0.000,P_C=0.006,OR=0.610;P=0.036,OR=0.794).GD patients with GO also showed a lower frequency of the rs3810936 CT genotype and the rs4979462 T allele than the controls(P=0.002,P_C=0.042,OR=0.621;P=0.041,OR=0.775).Inactive GO patients showed a lower frequency of the rs3810936 CT genotype than controls(P=0.002,P_C=0.042,OR=0.602),while GD females demonstrated a lower incidence of the T allele in rs4979462 and rs6478106 than the controls(P=0.015,OR=0.721;P=0.038,OR=0.760).Furthermore,GO females exhibited a lower rate of the rs4979462 T allele than the controls(P=0.018,OR=0.695).Conclusion:Our results suggest that TNFSF15 rs3810936 and rs4979462 polymorphisms are associated with the susceptibility of GO in a Han Chinese population.Additionally,rs3810936 may affect the activity of GO,and rs4979462 may correlate with the sexual dimorphism observed in GO.