KCNQ1基因单核苷酸多态性与妊娠期糖尿病的相关性

  目的  探讨电压依赖性钾离子通道(potassium voltage-gated channel, subfamily Q, member 1, KCNQ1)基因多态性与妊娠期糖尿病(gestational diabetes mellitus, GDM)发病风险的关系，为GDM的机制研究提供线索与依据。  方法  采用匹配的病例对照研究设计，病例组来自2012年3月1日—2014年7月30日在山西医科大学第一医院分娩的334名GDM孕妇，按年龄和居住地1∶1匹配334名健康对照，对研究对象进行DNA基因分型。在共显性、显性、隐性、相加等遗传模式下，通过Logistic回归分析模型分析KCNQ1基因的13个候选单核苷酸多态性(single nucleotide polymorphism, SNP)和GDM发病风险的关系，并采用HaploView软件分析单倍体与GDM之间的关系。  结果  在调整糖尿病家族史、孕前BMI且调整多重比较后，在共显性遗传模式下，rs4930000位点携带GG基因型的孕妇与携带AA基因型相比是发生GDM的危险因素(OR=3.37, 95% CI: 1.30~8.73, P=0.013)。rs163171位点携带GA基因型与AA基因型孕妇相比(OR=0.70, 95% CI: 0.50~0.98, P=0.037)，rs2074196位点携带CA基因型与携带CC基因型孕妇相比(OR=0.65, 95% CI: 0.46~0.91, P=0.012)，rs2237888位点携带GA基因型与GG基因型孕妇相比(OR=0.69, 95% CI: 0.49~0.98, P=0.037)，rs72847583位点携带CG基因型与携带CC基因型的孕妇相比(OR=0.63, 95% CI: 0.43~0.92, P=0.017)，发生GDM风险低，均是GDM的保护因素。在KCNQ1基因内由rs11023996、rs7924946组成的单倍体Block1 AA表型和由rs233446、rs2237893、rs151293、rs16318、rs163183与rs234852组成的单倍体Block2 CGACG表型与GDM的发病风险相关。  结论  KCNQ1基因位点多态性(rs4930000、rs163171、rs2074196、rs2237888、rs72847583)、单倍体Block1 AA表型与Block2 CGACG表型均与GDM的发病风险相关。

Association of KCNQ1 gene polymorphism with the risk of gestational diabetes

  Objective  This study aims to investigate the relationship between KCNQ1 (potassium voltage-gated channel, subfamily Q, member 1)gene polymorphism and the risk of gestational diabetes mellitus (GDM), and to provide clues for the study of the GDM mechanism.  Methods  We used a matched nested case-control study design, individuals including 334 gestational diabetes patients and 334 healthy controls. Confirmed 334 gestational diabetes cases and age and residence matched controls (1∶1) were enrolled. We examined 13 candidate single-nucleotide polymorphisms in the KCNQ1 gene and the risk of gestational diabetes. The associations were estimated in Co-dominant, Dominant, Recessive, and Alleles models. HaploView software was used to analyze the relationship between haplotype and gestational diabetes.  Results  After adjusting for family history of diabetes, pre-pregnancy body mass index, and multiple comparisons using false discovery rate method, in the co-dominant model, compared with AA genotype carriers, GG genotype carriers at rs4930000 had a higher risk of GDM (OR=3.37, 95% CI: 1.3-8.73, P=0.013). However, pregnant women who carried the rs163171GA genotype (OR=0.70, 95% CI: 0.50-0.98, P=0.037), rs2074196CA genotype (OR=0.65, 95% CI: 0.46-0.91, P=0.012), rs2237888 GA genotype (OR=0.69, 95% CI: 0.49-0.98, P=0.037) and rs72847583 CG genotype (OR=0.69, 95% CI: 0.49-0.98, P=0.017)had reduced risk of GDM. The haplotype Block1 AA phenotype is composed of rs11023996 and rs7924946 and the Block2 CGACG phenotype is composed of rs233446, rs2237893, rs151293, rs16318, rs163183, and rs234852 within the KCNQ1 gene were associated with the risk of gestational diabetes.  Conclusions  The polymorphisms of KCNQ1 (rs4930000、rs163171、rs2074196、rs2237888、rs72847583), the Block1 AA phenotype and Block2 CGACG phenotype are relevant genetic factors in a Chinese population with gestational diabetes.