Genetic polymorphisms of glucocorticoid receptor and their association with new-onset diabetes mellitus in kidney transplant recipients

Introduction: The variability in developing New-onset Diabetes Mellitus After Transplantation (NODAT), together with previously well-established interindividual variation in glucocorticoid sensitivity, led us to hypothesize that polymorphisms in the NR3C1 gene encoding glucocorticoid receptor may alter glucose balance in kidney transplant recipients. This study aimed to evaluate the association of three functional polymorphisms, BclI, N363S, and ER22/23EK, on the NR3C1 gene with NODAT in kidney allograft recipients.Methods: From Jun 2020 to July 2022 in Shiraz, 52 patients with NODAT (case group) and 52 non-diabetic kidney transplant recipients (control group) were randomly screened and recruited in this case-control study. The PCR-RFLP technique determined the genotypes of BclI, N363S, and ER22/23EK polymorphisms.Results: The allelic frequencies of the mutant alleles of BclI, N363S, and ER22/23EK polymorphisms in all pa-tients were 0.36, 0.03, and 0.009, respectively. BclI mutant genotypes (CG and GG) were significantly associated with an increased risk of NODAT (P = 0.016), while the two other polymorphisms disclosed no significant as-sociation with NODAT development. In the case group, no significant association was detected between the onset time of NODAT and studied polymorphisms, including BclI (P = 0.43), N363S (P = 0.30), and ER22/23EK. P value was not reported for the last polymorphism because all patients with NODAT had the wild-type genotype (GG/GG) and performing statistical analysis was not feasible. Among studied demographic/clinical/paraclinical variables, factors such as higher mean trough level of tacrolimus during the first month after transplantation and higher mean daily dose of prednisolone significantly linked with NODAT development.Conclusion: Our data suggested that BclI polymorphism significantly affects NODAT development among Iranian kidney allograft recipients.

Automated summary

This study aimed to evaluate the association between three functional polymorphisms (BclI, N363S, and ER22/23EK) on the NR3C1 gene and the development of NODAT in kidney transplant recipients. The results showed that the BclI mutant genotypes were significantly associated with an increased risk of NODAT.