Multidrug Resistant 1 (MDR1) C3435T and G2677T Gene Polymorphism: Impact on the Risk of Acute Rejection in Pediatric Kidney Transplant Recipients

Overview

Journal Ital J Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2023 May 17

PMID 37198710

Authors

Mai S Korkor

Tarek El-Desoky

Youssef M Mosaad

Doaa M Salah

Ayman Hammad

Affiliations

Soon will be listed here.

Abstract

Background: Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients.

Methods: Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls.

Results: In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation.

Conclusion: The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

Citing Articles

A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana.

Kwakyi E, Nartey E, Otabil M, Asiedu-Gyekye I, Ahorhorlu S, Bioma V BMC Res Notes. 2024; 17(1):210.

PMID: 39080672 PMC: 11288130. DOI: 10.1186/s13104-024-06868-8.

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