Chen Yan-yan, Li Guang-wei, Li Chun-mei, Huang Xiao-hong, Ju Zhen-yu, Sun Shu-xiang, Cai Hui, Hui Ru-tai
Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China.
Zhonghua Yi Xue Za Zhi. 2003 Jul 25;83(14):1229-32.
To investigate the relationship between G-protein beta(3) subunit (GNB(3)) gene polymorphism and essential hypertension, insulin resistance and obesity.
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.
(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 = 0.06). (2) The insulin sensitivity index [IAI = 1/(FPG x 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 = -0.3519, P = 0.0001), whereas this correlation was not significant in the CC genotype group (r = -0.0055, P = 0.931). The patients were divided into 2 groups according to the median of IAI. In the group with the IAL higher than the median (LnIAI = -5.0016 +/- 0.1830) the SBP of the CT/TT genotype carriers was significantly higher than that of the CC genotype carriers (146 +/- 1.84 mm Hg vs 132 +/- 5.19 mm Hg, P < 0.05). In the group with the IAI lower than the median [IAI(2) = -4.1625 +/- 0.3716] the SBP of the CT/TT genotype carriers was not significantly different from that of the CC genotype carriers (136 +/- 2.4 mm Hg vs 133 +/- 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.
CT and TT genotype of GNB(3) C825T was correlated with insulin sensitivity, blood pressure, and BMI. GNB(3) C825T gene enhances the hypertensive effect of insulin resistance.
探讨G蛋白β(3)亚基(GNB(3))基因多态性与原发性高血压、胰岛素抵抗及肥胖之间的关系。
采用简便方法测定376例个体(中国大庆地区187例高血压患者的第一代子代和189例非高血压患者的第一代子代)的空腹血糖(FPG)、空腹胰岛素(Ins)、血脂谱和纤维蛋白原(Fib),并通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)和测序检测GNB(3)基因多态性。运用单因素相关分析以及SAS软件包进行多因素回归分析,研究GNB(3)基因多态性与高血压、胰岛素抵抗的关系。
(1)高血压患者第一代子代中GNB(3) C825T的CT/TT基因型频率显著高于非高血压患者第一代子代(0.78:0.69,P = 0.06)。(2)CT和TT基因型组的胰岛素敏感性指数[IAI = 1/(FPG×FINS)]显著低于CC基因型组。其血压和体重指数(BMI)显著高于CC基因型组。(3)CT/TT基因型组中IAI与收缩压(SBP)呈负相关(r = -0.3519,P = 0.0001),而在CC基因型组中这种相关性不显著(r = -0.0055,P = 0.931)。根据IAI中位数将患者分为两组。在IAI高于中位数的组(LnIAI = -5.0016±0.1830)中,CT/TT基因型携带者的SBP显著高于CC基因型携带者(146±1.84 mmHg对132±5.19 mmHg,P < 0.05)。在IAI低于中位数的组[IAI(2) = -4.1625±0.3716]中,CT/TT基因型携带者的SBP与CC基因型携带者无显著差异(136±2.4 mmHg对133±2.0 mmHg,P > 0.05)。舒张压的比较结果相似。(4)在控制年龄和性别后,无高血压家族史的CT/TT基因型携带者中IAI与SBP呈负相关(r = -0.4864,P = 0.001),然而,在CC基因型携带者中未发现这种相关性。
GNB(3) C825T的CT和TT基因型与胰岛素敏感性、血压和BMI相关。GNB(3) C825T基因增强了胰岛素抵抗的高血压效应。