Correlation between CTLA-4 and CD40 gene polymorphisms and their interaction in graves' disease in a Chinese Han population

Background: Single-nucleotide polymorphism (SNP) haplotype and SNP-SNP interactions of CTLA-4 and CD40 genes, with susceptibility to Graves' disease (GD), were explored in a Chinese Han population. Methods: SNP were genotyped by high resolution melting (HRM). Use the method of Pearson chi 2 test and Logistic regression for the association between single SNP and Graves' disease. Using the method of chi 2 test and Multifactor Dimensionality Reduction (MDR) to analysis the haplotype frequency distribution, the interaction of SNPs respectively. Results: Genotypic and allelic frequencies of SNP rs231775, rs3087243 and rs1883832 were statistically different between controls and GD (p < 0.05). Mutant allelic frequency of G rs231775 was higher, and A and T allelic frequencies of rs3087243 and rs1883832 were lower in GD than in controls (P < 0.05). In CTLA-4 rs1024161, rs5742909, rs231775, rs231777, rs231779, rs3087243 and rs11571319 showed D' < 50% and r(2) < 0.3 among each SNP. We identified six commonly found haplotypes; TCGCTGC was associated with the highest GD risk (OR = 2.565) and TCACTAC the lowest (OR = 0.096). MDR analysis indicated interactions among the rs231775 GG, rs231779 TT and rs3087243 GG genotypes in CTLA-4 might increase GD risk by 2.53-fold (OR= 2.53). Conclusion: CTLA-4 and CD40 were associated with GD incidence in a Chinese Han population. The TCGCTGC and TCAC TAC haplotypes in the CTLA-4 gene, were risk and protective factors for Graves'disease respectively. Interactions among the SNPs of rs231775, rs231779 and rs3087243 significantly increase the susceptibility to GD.