Endothelin-1 rs5370 gene polymorphism among children with primary nephrotic syndrome: A single center study.

Hypothesis: Primary nephrotic syndrome is a common renal pediatric disorder. We investigated allelic frequencies and genotypes of Endothelin (EDN1) rs5370 polymorphism among children with primary NS. Methods: A case control study was conducted in Mansoura University Children’s Hospital, Egypt during the period from December 2015 to January 2018. We included 50 steroid sensitive NS (SSNS) and 50 steroid resistant NS (SRNS) in addition to 100 healthy controls. All patients were assessed clinically and investigated for serum albumin, cholesterol, creatinine and urea, and 24-h urinary protein. We investigated all groups for EDN1 rs5370 genotypes (GG, GT and TT) and alleles (G and T) using polymerase chain reaction amplification-refractory mutation system. We used chi-square test to verify agreement of allelic frequencies and genotypes of EDN1 rs5370 polymorphism with Hardy–Weinberg equilibrium (p ˃ 0.05 for each group). We used Fisher exact, chi-square and Kruskal–Wallis tests. We presumed statistical significance at p &lt; 0.05. Results: We found that GG genotype frequency was significantly higher in NS group than control group (p = 0.02) while GT genotype was the most frequent in control group (88%, p = 0.001). EDN1 rs5370 alleles showed insignificant differences between NS group and control (p = 0.69). GG genotype was found to be significantly higher among SSNS group when compared to SRNS and control groups (p = 0.03). Insignificant difference was detected in allelic frequency between SSNS, SRNS and control groups (p = 0.89). GG genotype was associated with hypertension among NS children (p &lt; 0.001) while GT genotype was associated with normal blood pressure (p = 0.007). We found insignificant differences between the studied genotypes and serum cholesterol level or renal histopathology. Conclusions: EDN1 rs5370 polymorphism may predispose to primary NS in children and affects the steroid therapy response and blood pressure values.研究假说：原发性肾病综合征（primary nephrotic syndrome, PNS）是儿童常见的肾脏疾病。本研究旨在探讨原发性肾病综合征（NS）患儿内皮素1（Endothelin, EDN1）rs5370基因多态性的等位基因频率与基因型分布。方法：本研究为病例对照研究，于2015年12月至2018年1月在埃及曼苏拉大学儿童医院开展。共纳入50例激素敏感型肾病综合征（steroid sensitive NS, SSNS）患者、50例激素抵抗型肾病综合征（steroid resistant NS, SRNS）患者，以及100名健康对照者。所有受试者均接受临床评估，并检测血清白蛋白、胆固醇、肌酐、尿素水平及24小时尿蛋白定量。采用聚合酶链反应-扩增阻滞突变系统（polymerase chain reaction amplification-refractory mutation system, PCR-ARMS）检测所有研究对象的EDN1 rs5370基因型（GG、GT、TT）及等位基因（G、T）。采用卡方检验验证EDN1 rs5370多态性的等位基因频率与基因型分布是否符合哈迪-温伯格平衡（各组均p>0.05）。此外，采用Fisher确切概率法、卡方检验及Kruskal-Wallis检验进行统计分析，以p<0.05作为差异具有统计学意义的判定标准。结果：本研究发现，肾病综合征组的GG基因型频率显著高于对照组（p=0.02）；而GT基因型在对照组中最为常见（占比88%，p=0.001）。EDN1 rs5370的等位基因频率在肾病综合征组与对照组之间无显著差异（p=0.69）。与SRNS组及对照组相比，SSNS组的GG基因型频率显著更高（p=0.03）。SSNS、SRNS组与对照组之间的等位基因频率无显著差异（p=0.89）。GG基因型与肾病综合征患儿的高血压症状显著相关（p<0.001），而GT基因型则与正常血压状态相关（p=0.007）。未观察到研究涉及的基因型与血清胆固醇水平或肾脏病理组织学结果存在显著关联。结论：EDN1 rs5370基因多态性可能增加儿童原发性肾病综合征的发病风险，并影响患儿的激素治疗应答及血压水平。