评估孟加拉国儿童肾病综合征患者中 和 基因多态性与泼尼松抵抗的关联：一种基因型和单倍型方法。
Assessment of the Link of and gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach.
机构信息
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
Department of Pharmacy, Stamford University Bangladesh, 51, Siddeswari Road, Dhaka 1217, Bangladesh.
出版信息
J Adv Res. 2021 Feb 17;33:141-151. doi: 10.1016/j.jare.2021.02.001. eCollection 2021 Nov.
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 (1236C > T, 2677G > T, 3435C > T), (rs10482634, rs6877893), and (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 and GA haplotype of 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 and gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.
简介
肾病综合征是一种常见的儿科肾脏疾病。对几种遗传多态性的研究表明，它们对患者对类固醇的耐药性影响不一致。
目的
本研究旨在确定 （1236C>T、2677G>T、3435C>T）、 （rs10482634、rs6877893）和 （CYP3A5*3）基因多态性以及社会人口学和临床病理参数与儿童肾病综合征患者泼尼松龙耐药风险之间的关联。
方法
对 180 例肾病综合征患者进行病例对照分析。其中，30 例患者被归类为泼尼松龙耐药组，150 例患者被归类为泼尼松龙敏感组。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）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著相关（p>0.05）。2677G>T 的 GT 杂合子与泼尼松龙耐药的发生显著相关（OR=3.9，p=0.034）。对于 3435C>T，TC 杂合子和 TT 突变纯合子基因型存在统计学意义（OR=0.38，p=0.047；OR=3.06，p=0.038）。对于 rs10482634 多态性，AG 杂合子和 AG+GG 基因型与泼尼松龙耐药显著相关（OR=2.40，p=0.033；OR=2.36，p=0.034）。我们没有发现 rs6877893 和 CYP3A53 多态性与泼尼松龙耐药风险相关（p>0.05）。和 rs6877893 与 CYP3A53 多态性与泼尼松龙耐药风险相关（p>0.05）。和 rs6877893 与 CYP3A5*3 多态性与泼尼松龙耐药风险相关（p>0.05）。还发现 与 基因的 CTC 和 TGT 单倍型以及 基因的 GA 单倍型与儿科泼尼松龙耐药的风险增加相关（OR=4.47，p=0.0003；OR=2.71，p=0.03；OR=4.22，p=0.022，连续）。我们还观察到不同的社会人口学和临床病理因素与儿童肾病综合征中泼尼松龙耐药的相关性。
结论
我们的研究结果表明，与泼尼松龙耐药性相关的 基因多态性与儿童肾病综合征有关。
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