候选基因单核苷酸多态性与天津汉族人群甲状腺功能减退症相关性研究

Association between single nucleotide polymorphism loci of candidate gene and hypothyroidism in Tianjin Han population

目的:探索候选SNP位点与天津汉族人群甲状腺功能减退症(甲减)易感性的关系,寻找影响甲状腺功能的SNP位点。方法:采用病例对照研究,在天津地区共收集336例甲减病例和328例体检健康的对照人群,收集静脉血5 m L,采用Sequenom Mass ARRAY技术对PTC、VAV3、FOXE1、KIT、CCBE1基因及其附近区域上的8个位点进行基因分型。结果:基于等位基因的性别分层分析显示,在男性中,仅VAV3基因的位点rs4915077与甲减的易感性显著相关,P=0.027。而在女性中,VAV3基因的rs1472565,KIT基因附近的rs17827152和CCBE1基因上的rs4940904位点与甲减的易感关联性极为显著,P分别为0.001,0.012和0.023。基于基因型性别分层分析显示,仅在女性中发现KIT基因的rs17827152与甲减有显著关联性,P=0.034。多因素Logistic回归分析显示,在男性中,rs4915077位点具有统计学意义(P=0.04),其回归模型的偏回归系数β=-0.544。在女性中,仅rs17827152位点具有统计学意义(P=0.011),偏回归系数β=-0.723。结论:在天津汉族男性中,VAV3基因的rs4915077位点多态性与甲减的易感性相关,而在女性中,VAV3基因的rs1472565,KIT基因的rs17827152和CCBE1基因的rs4940904位点多态性均与甲减的易感性相关。

Objective： To explore the relationship between the candidate single nucleotide polymorphism（SNPs） regulating thyroid function and the hypothyroidism（HT） susceptibility of Tianjin Han population, and to search the SNP loci which affecting the thyroid function. Methods： A case-control study was used and a total of 336 HT patients and 328 normal individuals were interviewed with 5 m L venous blood in Tianjin. The 8 SNP loci located in PTC, VAV3, FOXE1, KIT, CCBE1 genes were genotyped with Sequenom Mass ARRAY Technology. Results： Results of the alleles of gender stratification analysis showed that only rs4915077 in VAV3 gene was associated with HT, P =0.027 in male. However,among female the rs1472565 in VAV3 gene, rs17827152 in KIT gene and rs4940904 in CCBE1 were associated with HT susceptibility, and P values were 0.001, 0.012 and 0.023, respectively. Results of the genotypes of gender stratification analysis showed that only rs17827152 in KIT gene was associated with HT susceptibility, and P value was 0.034 in female. The logistic regression analysis showed that rs4915077 in VAV3 gene was statistically significant（P=0.04）, and the partial regression coefficient was-0.544 in male population. In female, only rs17827152 in KIT gene was statistically significant（P =0.011）, and the partial regression coefficient was-0.723. Conclusion： Rs4915077 in VAV3 gene is associated with HT susceptibility in Tianjin Han male and rs1472565 in VAV3 gene, rs17827152 in KIT gene and rs4940904 in CCBE1 are associated with HT susceptibility in female population.