Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS

X. Hong, H. Xing, Y. Yu, Y. Wen, Y. Zhang, S. Zhang, G. Tang, Xiping Xu

Research output: Contribution to journalArticle

Abstract

Nifedipine GITS has diuretic and natriuretic properties, which may enhance its antihypertensive efficacy. We assessed contributions of polymorphisms in the urea transporter-A gene (SLC14A2) to interindividual variations in blood pressure (BP) response to nifedipine treatment. 405 subjects from a single Chinese county received a single oral dose of 30 mg nifedipine GITS (gastrointestinal therapeutic system) daily for 16 days. We genotvped two SNPs in SLC14A2 and found significant associations for the Val227Ile (rs1123617) and Ala357Thr (rs3745009) polymorphisms with BP response to nifedipine treatment. After treatment, subjects with either Ala357/Thr357 or Thr357/Thr357 genotypes had significantly smaller mean changes in systolic BP (SBP) (β ± SE = -2.87 ± 1.24 mmHg, p = 0.020) and diastolic BP (DBP) (β ± SE = -1.69 ± 0.62 mmHg, p = 0.006) compared to those with the Ala357/Ala357 genotype. Subjects with either Val227/Ile227 or Ile227/Ile227 genotypes had significantly larger mean changes in SBP (β ± SE = 3.13 ± 1.19, p = 0.009) and DBP (β ± SE = 1.50 ± 0.60 mmHg, p = 0.013) compared with those with the Val227l Val227 genotype after treatment. Subjects carrying both the Ala357/Ala357 genotype in the Ala357Thr polymorphism and either Val227/Ile227 or Ile227/Ile227 genotypes in the Val227Ile polymorphism had the highest mean change in SBP and DBP. Our study supports the conclusion that polymorphisms in the SLC14A2 gene can predict the antihypertensive efficacy of nifedipine GITS.

Original languageEnglish (US)
Pages (from-to)3-10
Number of pages8
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume29
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Antihypertensive efficacy
  • Nifedipine GITS
  • SLC14A2 gene
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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