Endothelin-1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome.

Ruifeng Zhang,Juan Lv,Zhaowen Zhong,Yan Li,Suqin Zhou,Qianqian Peng,Tingting Yuan,Huandan Yang,Bingbing Zhu,Shan Qiu

doi:10.1002/jcla.23134

Ruifeng Zhang, Juan Lv + Show 8 more

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https://doi.org/10.1002/jcla.23134

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Abstract

BackgroundRecently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin‐1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS.MethodsSeven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age‐matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP‐SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS.ResultsIndependent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57‐0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study.ConclusionsThis study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

Highlights

Childhood nephrotic syndrome is a group of symptoms that indicate kidney damage, damage to the glomeruli, the tiny units within the kidney where blood is filtered, and results in the release of too much protein from the body into the urine.[1,2] Childhood primary nephrotic syndrome (CPNS) is the most common type of childhood nephrotic syndrome.[1,3] There are around 16 ~ 18 childhood primary nephrotic syndrome (CPNS) patients in every 100 000 children.[4]
All the six single nucleotide polymorphisms (SNPs) in EDN1 were selected with minor allele frequencies (MAF) >0.1 in Chinese population according to SNP data in dbSNP database
The C allele frequency of rs9296344 was higher in CPNS patients than in healthy children (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [confidence intervals (CIs)] = 0.57-0.88, P = .001)

Summary

Introduction

Childhood nephrotic syndrome is a group of symptoms that indicate kidney damage, damage to the glomeruli, the tiny units within the kidney where blood is filtered, and results in the release of too much protein from the body into the urine.[1,2] Childhood primary nephrotic syndrome (CPNS) is the most common type of childhood nephrotic syndrome.[1,3] There are around 16 ~ 18 CPNS patients in every 100 000 children.[4]. Recent studies suggested that genetic factors, such as single nucleotide polymorphisms (SNPs), might contribute to the susceptibility of CPNS.[5,6,7,8]. Endothelin-1 (EDN1) encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor, and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. The rs5370 single nucleotide polymorphisms (SNPs) of Endothelin-1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). Conclusions: This study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS

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