Introduction

Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids.

Objectives

This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome.

Methods

A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome.

Conclusion

Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

中文翻译：

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评估孟加拉小儿肾病综合征患者 ABCB1 和 NR3C1 基因多态性与泼尼松龙耐药的关系：基因型和单倍型方法

介绍

肾病综合征是一种常见的小儿肾脏疾病。对几种基因多态性的研究揭示了对患者对类固醇耐药性的不一致影响。

目标

本研究旨在确定ABCB1 (1236C > T, 2677G > T, 3435C > T)、NR3C1 (rs10482634, rs6877893) 和CYP3A5 (CYP3A5*3) 基因多态性以及社会人口学和临床病理学参数与肾病综合征患儿发生泼尼松龙耐药。

方法

对 180 例肾病综合征患者进行病例对照分析。其中，泼尼松龙耐药组30例，泼尼松敏感组150例。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行基因分型。

结果

未发现 1236C > T 多态性与泼尼松龙耐药风险显着相关（p > 0.05）。发现 2677G > T 的 GT 杂合子与泼尼松龙耐药性的发展显着相关（OR = 3.9，p = 0.034）。在 3435C > T 的情况下，在 TC 杂合和 TT 突变纯合基因型（分别为 OR = 0.38，p = 0.047；OR = 3.06，p = 0.038）与泼尼松龙耐药性观察到统计学上显着的关联。对于 rs10482634 多态性，AG 杂合和 AG+GG 基因型与泼尼松龙耐药显着相关（OR = 2.40，p = 0.033；OR = 2.36，p = 0.034，分别）。我们发现 rs6877893 和 CYP3A5*3 多态性与泼尼松龙耐药风险无关（p > 0.05）。ABCB1的 CTC 和 TGT 单倍型NR3C1和 GA 单倍型也与儿科强的松龙耐药风险增加相关（OR = 4.47，p = 0.0003；OR = 2.71，p = 0.03；和 OR = 4.22，p = 0.022，连续）。我们还观察了不同社会人口学和临床病理学因素与儿童肾病综合征泼尼松龙耐药的相关性。

结论

我们的研究结果显示ABCB1和NR3C1基因多态性与强的松龙耐药性儿科肾病综合征显着相关。