糖皮质激素受体的基因多态性及其与肾移植受者新发糖尿病的关联。

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

作者信息

Azadi Soha, Azarpira Negar, Roozbeh Jamshid, Ezzatzadegan-Jahromi Shahrokh, Raees-Jalali Ghanbar Ali, Foroughinia Farzaneh, Karimzadeh Iman

机构信息

Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Gene. 2023 Mar 10;856:147138. doi: 10.1016/j.gene.2022.147138. Epub 2022 Dec 24.

DOI:10.1016/j.gene.2022.147138

PMID:36574937

Abstract

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 patients 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 association 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.

摘要

引言

移植后新发糖尿病（NODAT）发展过程中的变异性，以及先前已确定的糖皮质激素敏感性个体间差异，使我们推测编码糖皮质激素受体的NR3C1基因多态性可能会改变肾移植受者的葡萄糖平衡。本研究旨在评估NR3C1基因上的三种功能性多态性，即BclI、N363S和ER22/23EK，与同种异体肾移植受者NODAT的相关性。

方法

2020年6月至2022年7月在设拉子，本病例对照研究随机筛选并招募了52例NODAT患者（病例组）和52例非糖尿病肾移植受者（对照组）。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术确定BclI、N363S和ER22/23EK多态性的基因型。

结果

所有患者中，BclI、N363S和ER22/23EK多态性突变等位基因的等位基因频率分别为0.36、0.03和0.009。BclI突变基因型（CG和GG）与NODAT风险增加显著相关（P = 0.016），而其他两种多态性与NODAT发展无显著相关性。在病例组中，未检测到NODAT发病时间与所研究的多态性之间存在显著相关性，包括BclI（P = 0.43）、N363S（P = 0.30）和ER22/23EK。由于所有NODAT患者均为野生型基因型（GG/GG），无法进行统计分析，因此未报告最后一种多态性的P值。在所研究的人口统计学/临床/辅助临床变量中，移植后第一个月他克莫司平均谷浓度较高和泼尼松龙平均每日剂量较高等因素与NODAT发展显著相关。