Abstract
BackgroundSingle-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.MethodsSNP were genotyped by high resolution melting (HRM). Use the method of Pearson χ2 test and Logistic regression for the association between single SNP and Graves’ disease. Using the method of χ2 test and Multifactor Dimensionality Reduction (MDR) to analysis the haplotype frequency distribution, the interaction of SNPs respectively.ResultsGenotypic 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 r2 < 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).ConclusionCTLA-4 and CD40 were associated with GD incidence in a Chinese Han population. The TCGCTGC and TCACTAC 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.
Highlights
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
The TCGCTGC and TCAC TAC haplotypes in the CTLA-4 gene, were risk and protective factors for Graves’disease respectively
The results show that CTLA-4 and CD40 are associated with GD incidence in a Chinese Han population and that interactions among rs231775, rs231779 and rs3087243 SNPs significantly increased the susceptibility to GD
Summary
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. The pathogenesis of GD is unclear; genome-wide association studies (GWAS) indicate that the genetic background of GD is decided by several genes with differential penetrance. GD is a complex disease that is associated with gene-gene and gene-environment interactions [1, 2]. Chen et al BMC Medical Genetics (2018) 19:171 irrelevant in the Japanese, Brazil and Lebanese populations [4, 6, 7]. Candidate gene analysis and GWAS unanimously confirmed that the CD40–1 C/T polymorphism located at 20q11.2-20q13 was stably associated with GD susceptibility [8,9,10]. The Kozak consensus sequence is a necessary nucleotide fragment in the initiation of translation of CD40, while the CC genotype and allele C can both increase mRNA translation efficiency of the CD40 gene and increase its expression by 15–32% [11, 12]
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