Genetic and epigenetic landscape of erectile dysfunction: a comprehensive review

Abstract

Erectile Dysfunction (ED) is a multifactorial condition with significant physical, psychological, and societal impacts, affecting approximately 24.2 % of men in the United States, with prevalence increasing with age. While lifestyle factors and comorbidities such as diabetes and cardiovascular diseases are well-established contributors, emerging evidence highlights the role of genetic predisposition in ED pathogenesis. This review evaluates the genetic architecture of ED, focusing on candidate genes, genome-wide association studies (GWAS), and epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs. A comprehensive search strategy was employed, targeting peer-reviewed articles published between 2000 and 2024 from databases such as PubMed, Google Scholar, Scopus, and Web of Science. Keywords included “erectile dysfunction,” “genetic profiling,” “epigenetics,” and “GWAS.” Studies were selected based on relevance, methodological rigor, and contributions to understanding genetic and epigenetic factors in ED. Findings reveal significant associations between ED and polymorphisms in genes such as NOS3, PDE5A, AR, and SHBG, as well as epigenetic modifications influencing endothelial function and hormonal regulation. GWAS have identified loci near SIM1 and other genes linked to vascular health and metabolic pathways. Despite advancements, limitations such as small effect sizes of genetic variants and underrepresentation of diverse populations persist. This review underscores the potential of genetic profiling to enhance early diagnosis, personalized treatment, and preventive strategies, bridging the gap between research and clinical practice in ED management.