Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Int J Mol Sci. 2022 Aug 29;23(17):9783. doi: 10.3390/ijms23179783.
The c.825C>T single-nucleotide polymorphism (rs5443) of the guanine nucleotide-binding protein subunit β3 (GNB3) results in increased intracellular signal transduction via G-proteins. The present study investigated the effect of the GNB3 c.825C>T polymorphism on cardiovascular events among renal allograft recipients posttransplant. Our retrospective study involved 436 renal allograft recipients who were followed up for up to 8 years after transplant. The GNB3 c.825C>T polymorphism was detected with restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The GNB3 TT genotype was detected in 43 (10%) of 436 recipients. Death due to an acute cardiovascular event occurred more frequently among recipients with the TT genotype (4 [9%]) than among those with the CC/CT genotypes (7 [2%]; p = 0.003). The rates of myocardial infarction (MI)−free survival (p = 0.003) and acute peripheral artery occlusive disease (PAOD)−free survival (p = 0.004) were significantly lower among T-homozygous patients. A multivariate analysis showed that homozygous GNB3 c.825C>T polymorphism exerted only a mild effect for the occurrence of myocardial infarction (relative risk, 2.2; p = 0.065) or acute PAOD (relative risk, 2.4; p = 0.05) after renal transplant. Our results suggest that the homozygous GNB3 T allele exerts noticeable effects on the risk of MI and acute PAOD only in the presence of additional nonheritable risk factors.
鸟嘌呤核苷酸结合蛋白亚基β3（GNB3）的 c.825C>T 单核苷酸多态性（rs5443）导致通过 G 蛋白增加细胞内信号转导。本研究调查了 GNB3 c.825C>T 多态性对移植后肾移植受者心血管事件的影响。我们的回顾性研究涉及 436 名接受肾移植的患者，他们在移植后最长 8 年的时间内接受了随访。使用限制性片段长度多态性（RFLP）聚合酶链反应（PCR）检测 GNB3 c.825C>T 多态性。在 436 名受者中检测到 GNB3 TT 基因型 43（10％）。TT 基因型受者（4 [9％]）因急性心血管事件死亡的发生率高于 CC/CT 基因型受者（7 [2％]；p = 0.003）。MI 无事件生存率（p = 0.003）和急性外周动脉闭塞性疾病（PAOD）无事件生存率（p = 0.004）均明显低于 T 纯合子患者。多变量分析表明，纯合 GNB3 c.825C>T 多态性仅对肾移植后心肌梗死（相对风险，2.2；p = 0.065）或急性 PAOD（相对风险，2.4；p = 0.05）的发生有轻度影响。我们的研究结果表明，在存在其他非遗传性危险因素的情况下，纯合 GNB3 T 等位基因仅对 MI 和急性 PAOD 的风险产生明显影响。
