2型糖尿病胰岛素抵抗和胆固醇酯转运蛋白基因多态性的关联研究

目的 探讨胆固醇酯转运蛋白(cholesteyl ester transfer protein，CETP)基因多态性与2型糖尿病胰岛素抵抗的关系。方法 采用聚合酶链反应和酶切电泳方法对108例2型糖尿病患者进行CETP-TaqIB基因型分型，同时测定血脂、空腹胰岛素、胰岛素敏感指数和胰岛素抵抗指数。结果 正常对照组与2型糖尿病组等位基因频率和基因型分布无统计学意义；2型糖尿病甘油三酯(triglyceride，TG)、总胆固醇(total cholesterol，TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol，LDL-C)和载脂蛋白B(apolipoprotein B，apoB)浓度各基因型间差异无统计学意义，而高密度脂蛋白胆固醇(high density lipoprotein cholesterol，HDL-C)、载脂蛋白A1(apolipoprotein A1，apoA1)、空腹胰岛素(fasting insulin，FINS)、胰岛素敏感性指数(insulin sensitivity index，ISI)和HOMA模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance，HOMA-IR)各基因型间差异有统计学意义，HDL-C、apoA，和ISI B2B2型显著高于B1B1型，FINS和HOMA-IR B2B2型显著低于B1B1型；以胰岛素敏感性指数和HOMA-模型胰岛素抵抗指数为因变量进行多元回归分析，ISI和HOMA-IR与体重指数、收缩压、TC、HDL及基因型分型密切相关。结论 CETP-Taq IB基因多态性与2型糖尿病脂代谢及胰岛素抵抗密切关联，可能是胰岛素抵抗的重要遗传因素。

Association between insulin resistance and cholesteryl ester transfer protein gene polymorphism in type 2 diabetes mellitus

OBJECTIVE: To study the association between cholesteryl ester transfer protein (CETP) gene polymorphism and insulin resistance in type 2 diabetes. METHODS: CETP-TaqIB gene was genotyped with polymerase chain reaction-restriction enzyme fragment polymorphism analysis in 108 patients with type 2 diabetes and in 60 normal controls. Plasma lipids, fasting insulin, insulin sensitivity index and insulin resistance index were determined in 108 patients with type 2 diabetes. RESULTS: The distribution of CETP-TaqIB genotypes and B1B2 allele frequency in the patients with type 2 diabetes were similar to that in general population. High density lipoprotein cholesterol (HDL-C), apolipoprotein A1(apoA1) and insulin sensitivity index (ISI) levels were significantly higher in B2B2 genotype than in B1B1 genotype. Fasting insulin (FINS) and Homeostasis model assessment-insulin resistance (HOMA-IR) levels were significantly lower in B2B2 genotype than in B1B1 genotype. No significant differences in triglyceride (TG), total cholesterol(TC),low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB) levels were observed among different CETP-TaqIB genotype groups. By multivariate analysis, the determinants of ISI and HOMA-IR were body mass index (BMI), TC, HDL-C and CETP-TaqIB genotype. CONCLUSION: The CETP-TaqIB genotype is independently associated with insulin resistance and lipid metabolism. It may be an important risk factor of insulin resistance in type 2 diabetes.