G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions.
G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions.
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非裔美国人中 G 蛋白偶联受体激酶 4 多态性和美托洛尔血压反应：性别特异性和相互作用。
DOI：
10.1038/ajh.2008.341
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发表时间：
2009-03
影响因子：
3.2
通讯作者：
Lipkowitz, Michael S.
中科院分区：
文献类型：
--
作者：
Bhatnagar, Vibha;TO'Connor, Daniel;Brophy, Victoria H.;Schork, Nicholas J.;Richard, Erin;Salem, Rany M.;Nievergelt, Caroline M.;Bakris, George L.;Middleton, John P.;Norris, Keith C.;Wright, Jackson;Hiremath, Leena;Contreras, Gabriel;Appel, Lawrence J.;Lipkowitz, Michael S.
非裔美国人高血压和共病负担不成比例。血压反应的药物遗传学标志物尚未明确定义。本研究探讨了非裔美国人早期高血压肾硬化患者中G蛋白偶联受体激酶4（GRK4）变异体与美托洛尔治疗后血压反应之间的关系。来自非裔美国人肾脏疾病和高血压研究（AASK）试验的参与者在三个GRK4多态性上进行了基因分型：R65L，A142V和A486V。使用按性别分层的考克斯比例风险模型来确定GRK4变体与达到平均动脉压（MAP）107 mm Hg的时间之间的关系，并对血压反应的其他预测因素进行调整。通过分析基因单倍型的影响和相邻位点的分层分析，探讨了这三种多态性之间的潜在相互作用。在随机分配至常规MAP（102 - 107 mm Hg）的男性中，A142V的风险比和95%置信区间为1.54（1.11 - 2.44; P = 0.0009）。A142V与R65/L65或L65/L65的风险比为2.14（1.35 - 3.39; P = 0.001）。单倍型分析是一致的，但不确定。A142V与女性血压反应之间没有关联。结果表明，GRK4 A142V和血压反应之间的性别特异性关系，在非洲裔美国男性早期高血压肾硬化症。GRK4 A142的男性如果有GRK4 L65变异，则对美托洛尔的反应较低。GRK4变异体的作用和对美托洛尔的血压反应应该在更大的临床试验中进行研究。
African Americans have a disproportionate burden of hypertension and comorbid disease. Pharmacogenetic markers of blood pressure response have yet to be defined clearly. This study explores the association between G-protein-coupled receptor kinase type 4 (GRK4) variants and blood pressure response to metoprolol among African Americans with early hypertensive nephrosclerosis. Participants from the African American Study of Kidney Disease and Hypertension (AASK) trial were genotyped at three GRK4 polymorphisms: R65L, A142V, and A486V. A Cox proportional hazards model, stratified by gender, was used to determine the relationship between GRK4 variants and time to reach a mean arterial pressure (MAP) of 107 mm Hg, adjusted for other predictors of blood pressure response. Potential interactions between the three polymorphisms were explored by analyzing the effects of gene haplotypes and by stratifying the analysis by neighboring sites. The hazard ratio with 95% confidence interval by A142V among men randomized to a usual MAP (102–107 mm Hg) was 1.54 (1.11–2.44; P = 0.0009). The hazard ratio by A142V with R65/L65 or L65/L65 was 2.14 (1.35–3.39; P = 0.001). Haplotype analyses were consistent but inconclusive. There was no association between A142V and blood pressure response among women. Results suggest a sex-specific relationship between GRK4 A142V and blood pressure response among African-American men with early hypertensive nephrosclerosis. Men with a GRK4 A142 were less responsive to metoprolol if they had a GRK4 L65 variant. The effect of GRK4 variants and blood pressure response to metoprolol should be studied in larger clinical trials.
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影响因子：
4.9
作者：
Bhatnagar, Vibha;O'Connor, Daniel T.;Lipkowitz, Michael S.
通讯作者：
Lipkowitz, Michael S.
DOI：
10.1073/pnas.062694599
发表时间：
2002-03-19
影响因子：
11.1
作者：
Felder, RA;Sanada, H;Jose, PA
通讯作者：
Jose, PA
影响因子：
1.9
作者：
Wang, Yaping;Li, Biao;Gu, Dongfeng
通讯作者：
Gu, Dongfeng
影响因子：
19.6
作者：
Watanabe, H;Xu, J;Felder, RA
通讯作者：
Felder, RA
DOI：
10.1016/s0197-2456(96)00081-5
发表时间：
1996-08-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Wright, JT;Kusek, JW;Glassock, R
通讯作者：
Glassock, R