Thorup Jorgen, Nordenskjöld Agneta, Hutson John M
aDepartment of Pediatric Surgery, Rigshospitalet bFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark cDepartment of Women's and Children's Health, Pediatric Surgery Unit and Center for Molecular Medicine, Karolinska Institutet dPediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden eDepartment of Pediatric Urology, Royal Children's Hospital fDouglas Stephens Surgical Research Laboratory, Murdoch Children's Research Institute, Melbourne gDepartment of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):227-32. doi: 10.1097/MED.0000000000000063.
The purpose of this study was to review and comment on recent original presentations dealing with genetic and environmental factors in the cause of hypospadias.
The heritability is definitely high and having an affected family member is the highest identified risk factor so far. Many candidate genes and polymorphisms have been suggested for hypospadias. Some associations with hypospadias were found, and many of these were replicated inconsistently as would be expected in a complex disorder affected by both genes and environment. The consistent association of hypospadias with low birth weight, maternal hypertension, and preeclampsia suggests that placental insufficiency is a major risk factor. Maternal exposure to chemical pollutants or endocrine disruptors in high concentrations related to selected occupations or geographic areas may be additional risk factors for hypospadias, especially in genetically predisposed individuals. So far, however, no environmental chemical pollutants or endocrine disruptor with a general common impact on the risk for hypospadias in most societies has been demonstrated.
A major point that should be considered regarding the action of environmental toxicants in inducing hypospadias is the cumulative effects of multiple low-dose exposures. Furthermore, interactions between genetic and environmental factors may help to explain nonreplication in genetic studies of hypospadias.
本研究旨在对近期有关尿道下裂病因中遗传和环境因素的原创性报告进行综述和评论。
尿道下裂的遗传度肯定很高，有一名患病家庭成员是目前已确定的最高风险因素。已经提出了许多与尿道下裂相关的候选基因和多态性。发现了一些与尿道下裂的关联，其中许多关联的重复性不一致，这在受基因和环境共同影响的复杂疾病中是可以预料的。尿道下裂与低出生体重、母亲高血压和先兆子痫之间的一致关联表明胎盘功能不全是一个主要风险因素。母亲在与特定职业或地理区域相关的高浓度环境中接触化学污染物或内分泌干扰物可能是尿道下裂的额外风险因素，特别是在具有遗传易感性的个体中。然而，到目前为止，尚未证实有任何环境化学污染物或内分泌干扰物会对大多数社会中尿道下裂的风险产生普遍的共同影响。
在考虑环境毒物诱发尿道下裂的作用时，一个主要要点是多次低剂量接触的累积效应。此外，遗传和环境因素之间的相互作用可能有助于解释尿道下裂遗传研究中的非重复性。
