title: Arg347Cys polymorphism of alpha1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients.
abstract: Our objectives were to evaluate whether polymorphisms in the alpha1A- and beta2-adrenoceptor genes influence blood pressure response to nifedipine gastrointestinal therapeutic system (GITS). Hypertensive patients received daily treatment with an oral dosage of 30 mg nifedipine GITS for 16 days. Genotypes of the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene and the Arg16Gly and Gln27Glu polymorphisms in the beta2-adrenoceptor gene were determined by TaqMan single-nucleotide polymorphism genotyping assay. The sixteenth-day steady-state plasma concentration of nifedipine was measured using HPLC with UV detection. Multivariate linear regression was performed in a total of 447 patients to evaluate the effects of these polymorphisms on blood pressure response to nifedipine GITS. Patients carrying the Cys347 allele of the alpha1A-adrenoceptor gene had a greater systolic blood pressure reduction than did those carrying two Arg347 alleles of the alpha1A-adrenoceptor gene (32.5+/-14.0 versus 27.3+/-15.5 mm Hg, respectively, P=0.006). However, diastolic blood pressure reduction was not associated with the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene. In addition, no significant associations were observed between blood pressure reduction and two polymorphisms in the beta2-adrenoceptor gene. Our data suggest that the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene may be used to predict blood pressure response to nifedipine GITS in Chinese hypertensive patients.
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Hong
authors.forename: Haipeng
authors.initials: H
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C547713:ADRA1A protein, human; D018340:Receptors, Adrenergic, alpha-1; D014665:Vasodilator Agents; D009543:Nifedipine