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学科主题: 临床医学
题名:
Individual and joint association of alpha(1A)-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects
作者: Jiang, SQ; Mao, GY; Zhang, SC; Hong, XM; Tang, GF; Li, ZP; Liu, X; Zhang, Y; Wang, BY; Xu, XP; Wang, XB
刊名: CLINICAL PHARMACOLOGY & THERAPEUTICS
发表日期: 2005-09-01
DOI: 10.1016/j.clpt.2005.06.003
卷: 78, 期:3, 页:239-248
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: ANGIOTENSIN-II ; IN-VIVO ; PHARMACOLOGICAL CHARACTERIZATION ; CARDIAC MYOCYTES ; MESSENGER-RNAS ; SUBTYPE ; RAT ; ARTERY ; AORTA ; RESPONSIVENESS
英文摘要:

Background: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha(1A)-adrenergic receptor (alpha(1A)-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level.

Methods: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. Results. BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha(1A)-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, (alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours.

Conclusion: Our data suggest that the alpha(1A)-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha(1A)-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.

语种: 英语
WOS记录号: WOS:000231812000005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57986
Appears in Collections:北京大学第一临床医学院_心血管内科_期刊论文

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作者单位: 1.Anhui Med Univ, Inst Biomed, Hefei, Anhui, Peoples R China
2.Childrens Mem Res Ctr, Chicago, IL 60614 USA
3.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
4.Peking Univ, Hosp 1, Dept Cardiovasc Dis, Beijing 100871, Peoples R China
5.Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA
6.Childrens Mem Hosp, Mary Ann & J Milburn Smith Child Hlth Res Program, Chicago, IL 60614 USA
7.Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA

Recommended Citation:
Jiang, SQ,Mao, GY,Zhang, SC,et al. Individual and joint association of alpha(1A)-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects[J]. CLINICAL PHARMACOLOGY & THERAPEUTICS,2005,78(3):239-248.
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