Effect of CYP3A51/3 polymorphism on blood pressure in renal transplant recipients

Transplant Proc. 2012 Nov;44(9):2596-8. doi: 10.1016/j.transproceed.2012.09.047.

Abstract

Background: The cytochrome P450 3A5 (CYP3A5) enzyme has been implicated to determine blood pressure (BP) in humans. Different results have been reported concerning CYP3A5 gene polymorphisms and posttransplantation hypertension in kidney recipients. Our objective was to investigate whether CYP3A5 1/3 polymorphism was associated with ambulatory BP among a population of renal transplant recipients receiving the calcineurin inhibitor tacrolimus for immunosuppression.

Methods: Sixty primary kidney transplant recipients undergoing treatment with tacrolimus were genotyped for the CYP3A5 1/3 polymorphism. We analysed the association of the CYP3A5 alleles with ambulatory systolic and diastolic BP measured at 6 and 24 months posttransplantation.

Results: We observed that 23.3% of the patients were CYP3A5 1 carriers and 76.7% were homozygous for CYP3A5 3. CYP3A5 1 carriers showed higher adjusted systolic BP and diastolic BP at 6 and 24 months posttransplantation, and they were prescribed more antihypertensive drugs compared with non CYP3A5 1 carrier patients, albeit not significant. No significant differences were found comparing the distribution of the hypertension classes.

Conclusion: We did not observe a significant association of CYP3A5 1/3 polymorphism with posttransplantation hypertension, although there were some differences in BP associated with the presence of the CYP3A5 1 allele.

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure Monitoring, Ambulatory
  • Blood Pressure* / drug effects
  • Calcineurin Inhibitors
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy
  • Hypertension / enzymology
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Tacrolimus / metabolism
  • Tacrolimus / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus