非裔美国人肾脏疾病与高血压研究中ADRB2（rs2053044）基因多态性与血管紧张素转换酶抑制剂血压反应的关联

Association of the ADRB2 (rs2053044) polymorphism and angiotensin-converting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension.

作者信息

Anthony Ericha G, Richard Erin, Lipkowitz Michael S, Bhatnagar Vibha

机构信息

aGraduate School of Public Health, San Diego State University bDepartment of Family Medicine and Public Health, University of California San Diego cDepartment of Veterans Affairs, Health Services Research and Development, San Diego, California dDepartment of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia, USA.

出版信息

Pharmacogenet Genomics. 2015 Sep;25(9):444-9. doi: 10.1097/FPC.0000000000000154.

DOI:10.1097/FPC.0000000000000154

PMID:26111150

Abstract

AIM/OBJECTIVES/BACKGROUND: Hypertension is a risk factor for cardiovascular and kidney disease and is most prevalent in African-American adults. The renin-angiotensin-aldosterone system is integral in blood pressure regulation; angiotensin-converting enzyme inhibitors such as ramipril are first-line treatment options. As decreases in angiotensin result in catecholamine release, β-adrenergic receptor (ADRB) polymorphisms may influence blood pressure response to ramipril.

METHODS

Associations between ADRB polymorphisms and blood pressure response to ramipril were analyzed in the African American Study of Kidney Disease and Hypertension, a randomized clinical trial. A total of 336 participants were included in this analysis. Six polymorphisms were analyzed here: (a) ADRB1 rs1801252 (Ser49Gly) and rs1801253 (Gly389Arg); and (b) ADRB2 rs2053044, rs1042711, rs1042713 (Arg16Gly), and rs1042714 (Gln27Glu). Time to reach a mean arterial pressure (MAP) of 107 mmHg within the first 60 days after randomization was studied using Kaplan-Meier and Cox proportional hazards modeling for univariate and adjusted analyses.

RESULTS

Genotypes at rs2053044, upstream from the ADRB2 5' untranslated region, were associated with time to reach target MAP among those randomized to the usual treatment group. Participants with the GG genotype achieved target MAP on average 12.2 days (38.1%) later than in comparison with those with the A allele (P=0.01). After adjusting for covariates, those with the AA/AG genotype had 2.09 greater odds of reaching MAP of 107 mmHg or less within 60 days of treatment in comparison with those with a GG genotype (hazard ratio=2.09, 95% confidence interval=1.21-3.60).

CONCLUSION

Results suggest that ADRB2 rs2053044 genotypes may be a determinant of blood pressure response to ramipril. Additional studies are needed to clarify the effect of rs2053044 and other 5' untranslated region polymorphisms on gene expression and blood pressure response to angiotensin-converting enzyme inhibitors.

摘要

目的/目标/背景：高血压是心血管疾病和肾脏疾病的危险因素，在非裔美国成年人中最为普遍。肾素-血管紧张素-醛固酮系统在血压调节中不可或缺；赖诺普利等血管紧张素转换酶抑制剂是一线治疗选择。由于血管紧张素的减少会导致儿茶酚胺释放，β-肾上腺素能受体（ADRB）基因多态性可能会影响对赖诺普利的血压反应。

方法

在一项随机临床试验——非裔美国人肾脏疾病与高血压研究中，分析了ADRB基因多态性与对赖诺普利的血压反应之间的关联。本分析共纳入336名参与者。这里分析了6种多态性：（a）ADRB1 rs1801252（Ser49Gly）和rs1801253（Gly389Arg）；以及（b）ADRB2 rs2053044、rs1042711、rs1042713（Arg16Gly）和rs1042714（Gln27Glu）。使用Kaplan-Meier法和Cox比例风险模型进行单变量和校正分析，研究随机分组后前60天内达到平均动脉压（MAP）107 mmHg的时间。

结果

ADRB2 5'非翻译区上游的rs2053044基因型与随机分配到常规治疗组的患者达到目标MAP的时间相关。GG基因型参与者达到目标MAP的平均时间比A等位基因参与者晚12.2天（38.1%）（P = 0.01）。在调整协变量后，与GG基因型参与者相比，AA/AG基因型参与者在治疗60天内达到107 mmHg或更低MAP的几率高2.09倍（风险比 = 2.09，95%置信区间 = 1.21 - 3.60）。