Chen Xiaoming, Hu Zhuoqing, Li Wei, Wu Ping, Liu Meilian, Bao Liwen, Wu Meifen, Fang Shuo, Xiong Wei, Chen Manyang, Wu Ge
Department of Endocrinology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
Gene. 2015 Aug 10;567(2):154-8. doi: 10.1016/j.gene.2015.04.074. Epub 2015 Apr 30.
The aim of this study was to investigate whether a genetic combined effect exists between CD40-1C>T and CTLA-4+6230G>A (CT60) polymorphisms and whether the combined effect renders susceptibility to Graves' disease (GD). We recruited 260 patients with GD and 248 healthy controls. Single nucleotide polymorphisms were genotyped by polymerase chain reaction-high resolution melting. Genetic polymorphisms related to GD were identified, levels of thyroid stimulating hormone receptor antibodies (TRAb) were measured, and genetic interactions were assessed by logistic regression analysis. Significant difference in allele and genotype frequency of CD40-1C>T polymorphism was observed between the patients and control subjects (P<0.001, 0.002 respectively). As for CTLA-4+6230G>A polymorphism, significant difference was observed only in allele frequencies between the patient and control groups (P=0.014). Moreover, a significant combined effect was presented in CD40-1C>T and CTLA-4+6230G>A polymorphism (P=0.020), and all, but one, combination CC-genotype of CD40-1C>T and GG-genotype of CTLA-4+6230G>A polymorphism has 54% lower risk of GD development than subjects with the CC and GG genotypes (OR=0.46, 95% CI=0.25-0.84). In newly onset GD group, neither single SNP (CD40-1C>T or CTLA-4+6230G>A polymorphism) nor their combined effect was showed a significant association with TRAb concentration (all P>0.05). Our findings suggest a possible additive combined effect between CD40-1C>T and CTLA4+6230G>A polymorphisms in the development of GD.
本研究旨在探讨CD40基因-1C>T多态性与细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因+6230G>A（CT60）多态性之间是否存在基因联合效应，以及这种联合效应是否会导致格雷夫斯病（GD）易感性增加。我们招募了260例GD患者和248名健康对照者。通过聚合酶链反应-高分辨率熔解曲线法对单核苷酸多态性进行基因分型。鉴定与GD相关的基因多态性，检测促甲状腺激素受体抗体（TRAb）水平，并通过逻辑回归分析评估基因相互作用。患者组与对照组之间CD40基因-1C>T多态性的等位基因频率和基因型频率存在显著差异（分别为P<0.001和0.002）。至于CTLA-4基因+6230G>A多态性，仅在患者组与对照组之间的等位基因频率上观察到显著差异（P=0.014）。此外，CD40基因-1C>T多态性与CTLA-4基因+6230G>A多态性之间存在显著的联合效应（P=0.020），除一种组合外，CD40基因-1C>T的CC基因型与CTLA-4基因+6230G>A的GG基因型组合发生GD的风险比CC和GG基因型个体低54%（比值比=0.46，95%置信区间=0.25-0.84）。在初发GD组中，单个单核苷酸多态性（CD40基因-1C>T或CTLA-4基因+6230G>A多态性）及其联合效应均与TRAb浓度无显著相关性（所有P>0.05）。我们的研究结果提示，CD40基因-1C>T多态性与CTLA-4基因+6230G>A多态性在GD发生过程中可能存在累加联合效应。
