Ajayi Ayodeji Folorunsho, Oyowvi Mega Obukohwo, Akanbi Grace Bosede, Ajayi Lydia Oluwatoyin, Ayomide Jonathan Jegede
Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Anchor Biomed Research Institute, Ogbomoso, Oyo State, Nigeria.
Biochem Genet. 2025 Jul 15. doi: 10.1007/s10528-025-11199-9.
This study examines the genetic susceptibility and pathogenesis of hypospadias. Hypospadias is a birth defect of the urethra where the urinary opening is on the underside of the penis rather than at the tip. This study aims to identify the genetic basis of this defect and, by extension, improve our understanding of the biological pathways involved in its pathogenesis. Novel genetic loci and variants associated with hypospadias were identified through case-control studies in Europe and North America and, more recently, through large-scale genome-wide association studies (GWAS). The identified genetic loci may be crucial in gene regulation or expression associated with penile development, or they may increase susceptibility to environmental factors that increases the occurrence of hypospadias. Moreover, analysis of associated variants revealed that most variants have a modest effect on hypospadas risk. To better understand the underlying biological pathways, data-driven approaches such as gene expression and epigenetic analysis are being used to identify gene networks and regulatory regions relevant to hypospadias pathogenesis. In conclusion, this study provides a comprehensive overview of genetic susceptibility and pathogenesis of hypospadias and highlights the need for further research into the role of genetic and environmental factors in the onset and progression of this defect.
本研究探讨尿道下裂的遗传易感性和发病机制。尿道下裂是一种尿道的先天性缺陷，尿道口位于阴茎腹侧而非顶端。本研究旨在确定该缺陷的遗传基础，并进而增进我们对其发病机制中所涉及生物学途径的理解。通过欧洲和北美的病例对照研究，以及最近通过大规模全基因组关联研究（GWAS），确定了与尿道下裂相关的新的基因位点和变异。所确定的基因位点可能在与阴茎发育相关的基因调控或表达中起关键作用，或者它们可能增加对环境因素的易感性，从而增加尿道下裂的发生率。此外，对相关变异的分析表明，大多数变异对尿道下裂风险的影响较小。为了更好地理解潜在的生物学途径，正在使用诸如基因表达和表观遗传分析等数据驱动方法来识别与尿道下裂发病机制相关的基因网络和调控区域。总之，本研究全面概述了尿道下裂的遗传易感性和发病机制，并强调需要进一步研究遗传和环境因素在该缺陷发生和发展中的作用。
