Individual and joint association of α1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects

Shanqun Jiang, Guangyun Mao, Shanchun Zhang, Xiumei Hong, Genfu Tang, Zhiping Li, Xue Liu, Yan Zhang, Binyan Wang, Xiping Xu, Xiaobin Wang

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the α1A-adrenergic receptor (α1A-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, α1A-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, α1A-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 β [± SE], 3.0 ± 1.0 mm Hg; P = .004) and at 6 hours (adjusted β, 3.0 ± 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted β, 5.6 ± 2.1 mm Hg; P = .006) and at 6 hours (adjusted β, 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 α1A-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 α1A-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.

Original languageEnglish (US)
Pages (from-to)239-248
Number of pages10
JournalClinical pharmacology and therapeutics
Volume78
Issue number3
DOIs
StatePublished - Sep 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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