甾体 5-α-还原酶 2 型（SRD5A2）基因 V89L 多态性与尿道下裂风险：一项荟萃分析。

Steroid 5-alpha-reductase type 2 (SRD5A2) gene V89L polymorphism and hypospadias risk: A meta-analysis.

机构信息

Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, Liaoning Province 110034, People's Republic of China.

出版信息

J Pediatr Urol. 2017 Dec;13(6):630.e1-630.e9. doi: 10.1016/j.jpurol.2017.05.022. Epub 2017 Jun 28.

DOI:10.1016/j.jpurol.2017.05.022

PMID:28713005

Abstract

BACKGROUND

Hypospadias is a common congenital malformation in males, in which the urethral orifice is found on the ventral side of the penis as a result of incomplete fusion of urethral folds. The etiology of hypospadias is poorly understood, and may be multifactorial, including genetic, endocrine and environmental factors. The steroid 5-alpha-reductase type 2 (SRD5A2) gene, which is mainly expressed in the ventral side of the urethra in the process of male genital development, plays an important role in urethral shaping.

OBJECTIVE

To investigate, with database searches of related published papers, whether SRD5A2 gene V89L polymorphism has an association with hypospadias risk.

METHODS

The following databases were searched for relevant papers, and all published case-control studies of hypospadias were used to perform a meta-analysis: PubMed, Embase, Springer Link, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. A quality assessment was performed using the Newcastle-Ottawa scale of a case-control study. To assess the strength of the association under various genetic models, odds ratio (OR) and its 95% confidence interval (CI) were calculated using fixed-effect or random-effects model according to the heterogeneity. Overall and stratified subgroup analyses, including ethnicity, source of controls, sample for DNA extraction, and hypospadias classification, were performed. All data were analyzed using Review Manager 5.3.

RESULTS

This analysis included six eligible case-control studies with 1130 cases and 1279 controls. Overall, there was a statistically significant association between hypospadias risk and V89L polymorphism for allele contrast (C vs G: OR 1.91, 95% CI 1.13-3.23), P = 0.02), codominant model (CC vs GG: OR 2.97, 95% CI 1.25-7.04, P = 0.01; GC vs GG: OR 2.36, 95% CI 1.35-4.13, P = 0.003), dominant model (GC + CC vs GG: OR 2.46, 95% CI 1.28-4.72, P = 0.007), and recessive model (CC vs GC + GG: OR 1.91, 95% CI 1.00-3.66, P = 0.05). Moreover, there was also a statistically significant association in some subgroups. The positive results are shown in the Summary Table.

CONCLUSION

This meta-analysis suggested that the V89L polymorphism definitely increases the risk of hypospadias, and the C allele is a genetic risk factor for hypospadias occurrence.

摘要

背景

尿道下裂是男性常见的先天性畸形，其尿道开口位于阴茎腹侧，是由于尿道褶融合不完全所致。尿道下裂的病因尚不清楚，可能是多因素的，包括遗传、内分泌和环境因素。甾体 5-α-还原酶 2 型（SRD5A2）基因主要在男性生殖器发育过程中尿道腹侧表达，在尿道形成中起重要作用。

目的

通过对相关已发表文献的数据库检索，探讨 SRD5A2 基因 V89L 多态性与尿道下裂风险的关系。

方法

检索了 PubMed、Embase、Springer Link、Cochrane 图书馆、中国知网（CNKI）、万方和维普等数据库，纳入了所有已发表的尿道下裂病例对照研究，进行荟萃分析。使用纽卡斯尔-渥太华量表对病例对照研究进行质量评估。根据异质性，采用固定效应或随机效应模型，计算各遗传模型下优势比（OR）及其 95%置信区间（CI），以评估关联的强度。进行了总体和分层亚组分析，包括种族、对照来源、DNA 提取样本和尿道下裂分类。所有数据均使用 Review Manager 5.3 进行分析。

结果

该分析纳入了 6 项符合条件的病例对照研究，共纳入 1130 例病例和 1279 例对照。总体而言，V89L 多态性与等位基因对比（C 对 G：OR 1.91，95%CI 1.13-3.23）、P=0.02）、共显性模型（CC 对 GG：OR 2.97，95%CI 1.25-7.04，P=0.01；GC 对 GG：OR 2.36，95%CI 1.35-4.13，P=0.003）、显性模型（GC+CC 对 GG：OR 2.46，95%CI 1.28-4.72，P=0.007）和隐性模型（CC 对 GC+GG：OR 1.91，95%CI 1.00-3.66，P=0.05）之间存在统计学显著关联。此外，在一些亚组中也存在统计学显著关联。阳性结果列于汇总表中。