一项关于血压和代谢表型与Gbeta3 C825T基因多态性相关性的流行病学研究。

An epidemiological study of blood pressure and metabolic phenotypes in relation to the Gbeta3 C825T polymorphism.

作者信息

Brand Eva, Wang Ji-Guang, Herrmann Stefan-Martin, Staessen Jan A

机构信息

Department of Endocrinology and Nephrology, Benjamin Franklin Medical Centre, Freie Universität Berlin, Germany.

出版信息

J Hypertens. 2003 Apr;21(4):729-37. doi: 10.1097/00004872-200304000-00016.

DOI:10.1097/00004872-200304000-00016

PMID:12658019

Abstract

BACKGROUND

The 825T allele of the G-protein beta(3)-subunit gene is associated with increased intracellular signalling and adipogenesis in experimental studies. We studied the C825T polymorphism in relation to blood pressure, obesity and intermediate phenotypes in a Caucasian population.

METHODS

We genotyped 737 men and 775 women (participation rate, 64.3%) enrolled in a Belgian population study. Dichotomous phenotypes were tested for association with the C825T polymorphism by Fisher's exact test and multiple logistic regression. For continuous traits, we used analysis of covariance and generalized estimating equations.

RESULTS

The T allele (39.7 versus 29.1%) and TT genotype (16.1 versus 7.7%) were more prevalent in obese men than in non-obese men (P < or = 0.01). TT homozygous men, compared with C allele carriers, had higher daytime ambulatory blood pressure (mean systolic/diastolic differences, 3.6/2.5 mmHg; P < or = 0.02), higher body weight (2.7 kg, P = 0.04), greater risk of obesity (risk ratio, 1.90; P = 0.005), increased triceps skinfold thickness (2.3 mm, P = 0.007), higher serum insulin concentration (4.1 mU/l, P = 0.006), more insulin resistance (P = 0.01), and increased erythrocyte count (0.11 x 1012 cells/l, P = 0.04) and haematocrit (0.9%, P = 0.02). In women, haematocrit and erythrocyte count were also higher (P < or = 0.03) in T allele carriers, but other phenotypes were not correlated with the C825T polymorphism.

CONCLUSION

Male and female carriers of the T allele at position 825 of the G-protein beta(3)-subunit gene have a slightly higher haematocrit and erythrocyte count. Male TT homozygotes have a higher blood pressure and are more obese and insulin-resistant than C allele carriers. We speculate that the higher blood pressure in TT homozygous men might arise via a metabolic pathway characterized by obesity and insulin resistance as well as via increased peripheral resistance secondary to the higher haematocrit.

摘要

背景

在实验研究中，G蛋白β(3)亚基基因的825T等位基因与细胞内信号传导增加及脂肪生成有关。我们在白种人群中研究了C825T多态性与血压、肥胖及中间表型的关系。

方法

我们对参与一项比利时人群研究的737名男性和775名女性（参与率为64.3%）进行了基因分型。通过Fisher精确检验和多因素逻辑回归分析二分表型与C825T多态性的关联。对于连续性性状，我们使用协方差分析和广义估计方程。

结果

T等位基因（39.7%对29.1%）和TT基因型（16.1%对7.7%）在肥胖男性中比在非肥胖男性中更常见（P≤0.01）。与C等位基因携带者相比，TT纯合子男性白天动态血压更高（平均收缩压/舒张压差值为3.6/2.5 mmHg；P≤0.02），体重更高（2.7 kg，P = 0.04），肥胖风险更大（风险比为1.90；P = 0.005），肱三头肌皮褶厚度增加（2.3 mm，P = 0.007），血清胰岛素浓度更高（4.1 mU/l，P = 0.006），胰岛素抵抗更强（P = 0.01），红细胞计数增加（0.11×10¹²个细胞/l，P = 0.04）和血细胞比容增加（0.9%，P = 0.02）。在女性中，T等位基因携带者的血细胞比容和红细胞计数也更高（P≤0.03），但其他表型与C825T多态性无关。