TCF7L2基因多态性与2型糖尿病合并高血压颈动脉内中膜厚度及僵硬度的关系

The correlation of TCF7L2 genetic polymorphisms with intimal -medial thickness and stiffness in the hypertension and type 2 diabetic patients

目的探讨2型糖尿病合并高血压患者颈动脉中内膜厚度及其僵硬度与TCF7L2基因多态性的关系。方法将872例2型糖尿病合并高血压的患者为研究对象,根据高频超声测定颈动脉内中膜厚度（IMT）、颈动脉僵硬度及颈动脉搏波传导速度（cPWV）等指标分为观察组（颈动脉的IMT〉1.0mm或局部有斑块存在者,cPWV〉12m/s）432例、对照组（颈动脉IMT≤1.0mm,cPWV≤12m/s）440例。同时选择空腹血糖、血压正常且无糖尿病及高血压家族史的健康体检者400例作为健康对照组。采用RT-PCR方法对TCF7L2基因多态性rs11196205、rs290487、rs11196218进行分型,并对各组研究对象的BMI、腰臀比、收缩压、舒张压、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-Ch）、低密度脂蛋白胆固醇（LDL-Ch）、胰岛素敏感指数（ISI）、糖化血红蛋白（HbA1c）进行比较。计算各位点等位基因及基因型频率,并进行Hardy-Weinberg平衡检测;应用χ2检验,比较各组等位基因频率分布差异,采用dominant模型比较各组基因型频率分布差异。结果rs290487基因分型分布,观察组与对照组（χ2=33.296,P〈0.05）及健康对照组与糖尿病组（χ2=100.801,P〈0.05）比较差异均有统计学意义,C及T等位基因频率观察组与对照组（χ2=16.280,P〈0.05）、健康对照组与糖尿病组间差异亦有统计学意义（χ2=27.190,P〈0.05）。而rs11196205、rs11196218的基因多态性差异无统计学意义（P〉0.05）。结论TCF7L2基因rs290487与2型糖尿病合并高血压颈动脉内中膜厚度及僵硬程度的发生发展密切相关,其C及T等位基因可能为导致2型糖尿病合并高血压患者颈动脉内中膜增厚、变硬的风险基因。Logistic回归分析提示收缩压、舒张压、TC、TG、LDL-Ch增高及HDL-Ch降低可能为导致2型糖尿病合并高血压颈动脉内中膜及僵硬度增加的风险因子,同时,可能提示了这些生化指标的升高为C及T等位基因变异的重要因素之一。

Objective To explore the relationship between TCF7L2 genetic polymorphisms with intimal -medial thickness （ IMT） , carotid arterial stiffness in patients of type 2 diabetes mellitus（ T2DM） with hypertension.Methods 872 patients of hypertension and T2DM were enrolled into this study, and they were divided into twogroups according to IMT, carotid arterial stiffness and cPWV： the observation group（ n =432, IMT 〉1. 0mm, cPWV 〉12m/ s） , the control group（ n =440, IMT≤1. 0mm, cPWV≤12m/ s） . Meanwhile, 400 healthy subjects（ normal fastinggluose, blood pressure, without diabetes and hypertension family history） were selected as the healthy group. Typedgene polymorphisms of TCF7L2 by RT - PCR, the body mass index（ BMI） , waist - hip ratio, systolic blood pressure,diastolic blood pressure, total cholesterol（ TC） , triglyceride（ TG） , high density lipoprotein cholesterol（ HDL - Ch） ,low - density lipoprotein cholesterol（ LDL - Ch） , insulin sensitivity index（ ISI） , glycated hemoglobin A1C（ HbA1c）between groups were compared. Calculated each allele and genotype frequencies and implemented Hardy - Weinbergequivalent test. The distributional differences of alleles frequencies between groups were analyzed by χ 2 test and genotype frequencies through dominant model. Results Distributional differences of rs290487 genotype frequencies hadstatistically significant differences in the observation group vs the control group（ χ 2 = 33. 296, P 〈 0. 05） and theT2DM group vs the normal group（ χ 2 = 100. 801, P 〈 0. 05） . Statistically significant differences existed in C and Talleles frequencies as well： the observation group vs the control group（ χ 2 = 16. 280, P 〈 0. 05） , the T2DM group vsnormal group（ χ 2 =27. 190, P 〈0. 05） . However, the gene polymorphisms of rs11196205 and rs11196218 showed nostatistically significant difference （ P 〉 0. 05） . Conclusion rs290487 involved in the development of T2DM withhypertension, C and T alleles might be the risk factors of increasing the IMT and carotid arterial stiffness levels inpatients of T2DM with hypertension. Logistic regression analysis revealed that the increase of SBP, DBP, TC, TG, LDL- Ch and decrease of HDL - Ch may be the risk factors of hypertension and diabetic patients. Meanwhile, it dedicatedthat the increase of those biochemical indexes might be the important elements which would lead to the gene variationsof C and T alleles.