[C825T polymorphism of the GNB3 gene codifying the G-protein beta3-subunit and cardiovascular risk].

Michelangelo Sartori, Emanuela Parotto, Giulio Ceolotto, Italia Papparella, Livia Lenzini, Lorenzo A Calò, Andrea Semplicini
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Abstract

Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure. A polymorphism (825C/T) in exon 10 of the GNB3 gene, that encodes for the beta3 subunit, has recently been described. The 825T allele is associated with alternative splicing of the gene and formation of a truncated but functionally active beta3 subunit. Carriers of the 825T allele appear to have an increased risk for hypertension, obesity, insulin-resistance and left ventricular hypertrophy. Moreover, 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic and with clonidine. GNB3 825T allele may be regarded as a potential genetic marker for a better definition of the risk profile of hypertensive subjects, but further studies are needed to precisely define the impact of T allele on the prognosis of such patients.

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[编码g蛋白β 3亚基的GNB3基因C825T多态性与心血管风险]。
高血压是一种常见的多因素疾病,是中风和心肌梗死等心血管事件的主要危险因素。异三聚体G蛋白的亚基是原发性高血压易感性和血压个体间变异的有吸引力的候选基因产物。最近已经描述了GNB3基因外显子10上编码β a3亚基的多态性(825C/T)。825T等位基因与基因的选择性剪接和截断但功能活跃的β 3亚基的形成有关。携带825T等位基因的人患高血压、肥胖、胰岛素抵抗和左心室肥厚的风险更高。此外,825T等位基因携带者对噻嗪类利尿剂和可乐定治疗有更强的降压反应。GNB3 825T等位基因可能是一个潜在的遗传标记,可以更好地定义高血压受试者的风险谱,但需要进一步的研究来精确定义T等位基因对高血压患者预后的影响。
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