A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals

Jasper J. Brugts, Aaron Isaacs, Moniek P.M. De Maat, Eric Boersma, Cock M. Van Duijn, K. Martijn Akkerhuis, Andre G. Uitterlinden, Jacqueline C.M. Witteman, Francois Cambien, Claudio Ceconi, Willem Remme, Michel Bertrand, Toshiharu Ninomiya, Stephen Harrap, John Chalmers, Stephen MacMahon, Kim Fox, Roberto Ferrari, Maarten L. Simoons, A. H.Jan Danser

研究成果: Contribution to journalArticle査読

40 被引用数 (Scopus)

抄録

Aims: To investigate whether genetic variation in the renin-angiotensin- aldosterone system (RAAS) and kallikrein-bradykinin pathways is related to hypertension and blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitor therapy in stable coronary artery disease (CAD) patients. Methods and Results: In 8907 stable CAD patients from the EUROPA trial, 52 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 12 candidate genes within the RAAS and kallikrein-bradykinin pathways were investigated for association with hypertension (defined as BP 160/95 mmHg or use of antihypertensives) and BP response to ACE inhibitors, during a 4-week run-in period. All analyses were adjusted for age, sex, body mass index and creatinine clearance and corrected for multiple testing. Results: Hypertension was present in 28.3% of the patients (n = 2526); median BP reduction after perindopril was 10/4 mmHg. Four polymorphisms, located in the ACE (rs4291), angiotensinogen (rs5049) and (pro)renin receptor (rs2968915; rs5981008) genes were significantly associated with hypertension in two vascular disease populations of CAD (EUROPA) and cerebrovascular disease (PROGRESS; n = 3571). A cumulative profile demonstrated a stepwise increase in the prevalence of hypertension, mounting to a 2-3-fold increase (P for trend <0.001). Similar associations on hypertension were observed for angiotensinogen in a healthy population (n = 2197). In addition, genetic polymorphisms were identified that significantly modified the BP reduction by ACE inhibitor therapy; however, the observed BP differences were small and did not remain significant after permutation analysis. Conclusion: This large genetic association study identified genetic determinants of hypertension in three cohorts of patients with vascular disease and healthy individuals.

本文言語英語
ページ(範囲)509-519
ページ数11
ジャーナルJournal of hypertension
29
3
DOI
出版ステータス出版済み - 3 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内科学
  • 生理学
  • 循環器および心血管医学

フィンガープリント

「A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル