Siffert Winfried
Department of Pharmacology, University Hospital, Hufelandstrasse 55, D-45122 Essen, Germany.
Curr Hypertens Rep. 2003 Feb;5(1):47-53. doi: 10.1007/s11906-003-0010-4.
The G-protein beta3 subunit (GNB3) C825T polymorphism was detected through a classical candidate gene approach using cell lines with enhanced G-protein activation from patients with essential hypertension. The 825T allele is associated with the expression of a shortened, functionally active splice variant of the G-protein beta3 subunit and enhanced intracellular signal transduction. Independent studies have confirmed an association of the 825T allele with hypertension in whites. Potential pathogenetic mechanisms comprise an increased susceptibility for obesity in 825T allele carriers and, potentially, increased responsiveness to vasoactive hormones. Both phenomena appear to be strongly influenced by lifestyle in the sense of a gene-environment interaction. Whether hypertensive 825T allele carriers are at increased risk for stroke and left ventricular hypertrophy remains controversial. Current studies try to define optimal therapy strategies for hypertensive 825T allele carriers.
采用经典候选基因方法，利用原发性高血压患者中具有增强G蛋白激活作用的细胞系，检测G蛋白β3亚基（GNB3）C825T多态性。825T等位基因与G蛋白β3亚基缩短的、功能活跃的剪接变体的表达以及增强的细胞内信号转导相关。独立研究已证实825T等位基因与白人高血压有关。潜在的致病机制包括825T等位基因携带者肥胖易感性增加，以及可能对血管活性激素的反应性增加。从基因-环境相互作用的角度来看，这两种现象似乎都受到生活方式的强烈影响。高血压825T等位基因携带者是否中风和左心室肥厚风险增加仍存在争议。目前的研究试图为高血压825T等位基因携带者确定最佳治疗策略。
