Lack of association between ACE I/D, NOS3 VNTR polymorphisms and drug toxicity of tacrolimus treated post-renal transplantation patients

Abstract

Introduction: Tacrolimus is the most commonly used calcineurin inhibitor for renal transplant individuals. Genetic factors play a major role in allografts by affecting blood pressure regulation, vascular proliferation and inflammatory responses. Objectives: The aim of this study was to evaluate a possible role of the ACE I/D and NOS3 VNTR polymorphisms in kidney transplantation patients treated with tacrolimus in the south Indian population. Patients and Methods: This study included 50 kidney transplant individuals and 100 unrelated healthy individuals from the general population as control. The genotyping was performed by polymerase chain reaction and electrophoresis. Genotypes were compared among cases and controls applying χ2 test. The difference in C/D ratios was compared using Mann–Whitney U test or Kruskal-Wallis test. Results: The ACE ID polymorphisms in different models [genetic (P=0.723), dominant (P=0.148) and recessive (P=0.652)] or allele model (P=0.455) did not differ significantly between the groups. Similarly, there was no significant difference for the NOS3 VNTR genotypes in genetic model (bb vs ba P=0.118; bb vs aa P=0.446), dominant model (bb vs ba+aa P=0.099) and allelic model (b vs a P=0.103). No significant difference was observed for ACE ID and NOS3 VNTR genotypes between the toxicity and non-toxicity groups. Furthermore, no significant association was observed for daily dose and concentration dose ratio for the studied polymorphisms. Conclusion: The present study revealed no significant association between cases and controls as well as toxicity and non-toxicity groups. Furthermore, there was no association between genotypes and daily dose and dose concentration.

Keywords

• tacrolimus
• ace i/d
• nos3 vntr
• transplantation
• polymorphisms
• end-stage renal disease
• calcineurin inhibitors