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首页> 外文期刊>Pharmacogenetics and genomics >Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses.
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Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses.

机译：alpha2C-肾上腺素能受体和G蛋白的遗传变异导致心血管压力反应的种族差异。

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OBJECTIVES: Cardiovascular responses to stressors are regulated by sympathetic activity, increased in black Americans, and associated with future cardiovascular morbidity. Our aim was to determine whether two functional variants in genes regulating sympathetic activity, a deletion in the alpha2C-adrenergic receptor (ADRA2C del322-325) and a G-protein beta3-subunit variant (GNB3 G825T), affect cardiovascular responses to physiologic stressors and contribute to their ethnic differences. METHODS: We measured heart rate and blood pressure responses to a cold pressor test (CPT) in 79 healthy participants (40 blacks, 39 whites), aged 25.7+/-5.3 years, and determined genotypes for the ADRA2C and GNB3 variants. We examined the response variables (increase in heart rate and blood pressure) in multiple linear regression analyses adjusting first for baseline measures, ethnicity, and other covariates, and then additionally for genotypes. RESULTS: Black participants had a greater heart rate response to CPT than whites [mean difference, 9.9 bpm; 95% confidence interval (CI), 4.1 to 15.6; P=0.001]. Both the ADRA2C del/del (15.8 bpm; 95% CI, 8.0-23.7; P<0.001) and GNB3 T/T genotypes (6.8 bpm; 95% CI, 0.9-12.7; P=0.026) were associated with greater heart rate response. After adjusting for genotypes, the ethnic difference was abrogated (1.3 bpm; 95% CI, -5.4-8.0; P=0.70), suggesting that the genetic variants contributed substantially to ethnic differences. CONCLUSION: Variation in genes that regulate sympathetic activity affects hemodynamic stress responses and contributes to their ethnic differences. This study elucidates how genetic factors may in part explain ethnic differences in cardiovascular regulation.
机译：目的：对应激源的心血管反应受到交感神经活动的调节，在美国黑人中增加，并且与未来的心血管疾病相关。我们的目的是确定调节交感神经活性的基因中的两个功能性变体，α2C-肾上腺素能受体的缺失（ADRA2C del322-325）和G蛋白β3-亚基变体（GNB3 G825T）是否影响心血管对生理应激源的反应和促进他们的种族差异。方法：我们测量了79名健康参与者（40名黑人，39名白人），年龄25.7 +/- 5.3岁的人对冷压力测试（CPT）的心率和血压反应，并确定了ADRA2C和GNB3变体的基因型。我们在多重线性回归分析中检查了响应变量（心率和血压升高），这些分析首先针对基线测量，种族和其他协变量进行调整，然后针对基因型进行调整。结果：黑人参与者对CPT的心率反应大于白人[平均差异，9.9 bpm; 95％置信区间（CI）为4.1至15.6; P ＝ 0.001]。 ADRA2C del / del（15.8 bpm; 95％CI，8.0-23.7; P <0.001）和GNB3 T / T基因型（6.8 bpm; 95％CI，0.9-12.7; P = 0.026）与更高的心率相关响应。在调整基因型后，种族差异被消除（1.3 bpm; 95％CI，-5.4-8.0; P = 0.70），这表明遗传变异对种族差异起了重要作用。结论：调节交感神经活动的基因变异影响血液动力学应激反应，并导致其种族差异。这项研究阐明了遗传因素如何部分解释心血管调节的种族差异。

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