Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Aging (Albany NY). 2021 May 7;13(10):13898-13908. doi: 10.18632/aging.202983.
Hypospadias is a common congenital genitourinary malformation characterized by ventral opening of the urethral meatus. As a member of the bone morphogenic protein antagonist family, has been identified as associated with susceptibility to hypospadias in the European population. The present study was designed to elaborate on the mutual relationship between replicated single-nucleotide polymorphisms (SNPs) and hypospadias in Asia's largest case-control study in the Southern Han Chinese population involving 577 patients and 654 controls. Our results demonstrate that the risk allele rs3743104[G] markedly increases the risk of mild/moderate and severe hypospadias (, 0.280.66). GTEx expression quantitative trait locus data revealed that the eQTL SNP rs3743104 has more associations of eQTL SNP rs3743104 and targets in pituitary tissues. Additionally, Bioinformatics and Luciferase Assays show that miR-182 is identified as a suppressor for expression, likely through regulation of its binding affinity to rs3743104 locus. In conclusion, the risk allele rs3743104[G] increases hypospadias susceptibility in mild/moderate and severe cases among the southern Han population. rs3743104 regulates expression by altering the binding affinity of miR-182 to their locus. Collectively, this study provides new evidence that rs3743104 is associated with an increased risk of hypospadias. These findings provide a promising biomarker and merit further exploration.
尿道下裂是一种常见的先天性泌尿生殖系统畸形，其特征为尿道外口位于阴茎腹侧。作为骨形态发生蛋白拮抗剂家族的一员， 已被确定与欧洲人群尿道下裂的易感性有关。本研究旨在阐述在亚洲最大的汉族人群病例对照研究中，重复单核苷酸多态性 (SNP) 与尿道下裂之间的相互关系，该研究纳入了 577 例患者和 654 例对照。我们的研究结果表明， 风险等位基因 rs3743104[G] 显著增加了轻度/中度和重度尿道下裂的发病风险 (OR=0.28, 95%CI=0.14-0.56)。GTEx 表达数量性状基因座数据显示，eQTL SNP rs3743104 与垂体组织中 基因的 eQTL SNP rs3743104 和 靶点有更多的关联。此外，生物信息学和荧光素酶报告基因实验显示，miR-182 被鉴定为 表达的抑制剂，可能通过调节其与 rs3743104 位点的结合亲和力来发挥作用。综上所述， 风险等位基因 rs3743104[G] 增加了南方汉族人群中轻度/中度和重度尿道下裂病例的易感性。rs3743104 通过改变 miR-182 与其位点的结合亲和力来调节 表达。总的来说，本研究提供了新的证据，表明 rs3743104 与尿道下裂风险增加相关。这些发现为尿道下裂提供了有前景的生物标志物，并值得进一步探索。
