G蛋白β_3亚单位C825T与高血压、胰岛素抵抗及肥胖的关联

Association between G-protein β_3 subunit (GNB_3) gene C825T polymorphism, hypertension, insulin resistance and obesity

目的 分析GNB3 基因C82 5T多态位点与原发性高血压、胰岛素抵抗和肥胖的关系。方法 对大庆地区 187个高血压家系和 189个非高血压家系的第一代子女进行空腹血糖、空腹胰岛素、血脂和纤维蛋白原等指标的测定 ,用聚合酶链反应 (PCR)扩增和酶切方法检测GNB3 C82 5T多态性 ,以多因素分析探讨各基因型与血压、胰岛素抵抗的关系。结果 (1)高血压家族史阳性组CT/TT基因型频率高于高血压家族史阴性组 (0 78∶0 6 9,P =0 0 6 )。 (2 )调整年龄、性别影响后 ,CT/TT基因型胰岛素敏感性显著低于CC基因型 ,血压、体重指数显著高于CC基因型。 (3)相关分析显示 ,CT和TT基因型组中 ,胰岛素敏感性与收缩压水平负相关 (r=- 0 35 19,P =0 0 0 0 1) ,CC基因型组则相关不显著 (r=- 0 0 0 5 5 ,P =0 93)。按胰岛素敏感指数中值将其分为两组后 ,胰岛素敏感性较差组中 ,CT和TT基因型者收缩压明显高于CC基因型者 (14 6mmHg± 1 84mmHgvs 132mmHg±5 19mmHg ,P <0 0 5 ) ;胰岛素敏感性较好组中 ,两者血压无显著差异。 (4 )无高血压家族史的第一代子女 ,CT和TT基因型组胰岛素敏感性也与收缩压呈负相关 (r=- 0 4 86 4 ,P =0 0 0 1) ,CC基因型组二者相关不显著。结论 GNB3 C82 5T基因型与胰岛素敏感性、血压水平及体?

Objectives To investigate the relationship between G-protein β 3 subunit (GNB 3 ) gene polymorphism and essential hypertension, insulin resistance and obesity Methods Fasting plasma glucose (FPG), fasting insulin (Ins), lipid profile, and fibrinogen (Fib) were determined by convenient methods and the polymorphism of GNB 3 was detected by PCR-RFLP and sequencing in 376 individuals 187 first generation offsprings of hypertensives and 189 first generation offsprings of nonhypertensives in Daqing, China. The relationship between GNB 3 polymorphism and hypertension, insulin resistance was analyzed by univariate correlation analysis, and multivariate regression analysis with SAS software package. Results (1) The frequency of CT/TT genotype of GNB 3 C825T was significantly higher in the first generation offsprings of the hypertensives than in the first generation offsprings of nonhypertensives (0.78∶0.69, P=006). (2) The insulin sensitivity index [IAI=1/(FPG×FINS)] in the CT and TT genotype groups was significantly lower than that in the group with CC genotype. The blood pressure and BMI were significantly higher than those of the CC genotype. (3) IAI was correlated negatively with SBP in CT/TT genotype group (r=-0.351 9, P=0.000 1), whereas this correlation was not significant in the CC genotype group (r= -0.005 5, P=0.93). The patients were divided into 2 groups according to the median of IAI. In the group with the IAI higher than the median (LnIAI=-5.001 6±0.183 0) the SBP of the CT/TT genotype carriers was significantly higher than that of the CC genotype carriers (146 mm Hg±1.84 mm Hg vs 132 mm Hg±5.19 mm Hg, P<0.05). In the group with the IAI lower than the median[IAI(2)=-4.1625±0371 6] the SBP of the CT/TT genotype carriers was not significantly different from that of the CC genotype carriers (136 mm Hg±2.4 mm Hg vs 133 mm Hg±2.0 mm Hg,P>0.05). The comparison of diastolic pressure showed the similar result. (4) IAI had negatively correlation with SBP in CT/TT genotype carriers without hypertensive family history after controlling age and sex (r=-0.4864 P=0.001), however, such correlation was not found in CC genotype carriers. Conclusion CT and TT genotype of GNB 3C825T was correlated with insulin sensitivity, blood pressure, and BMI. GNB 3825T gene enhances the hypertensive effect of insulin resistance.