A contribution of genetic factors to the development of stress urinary incontinence (SUI) is broadly acknowledged. This study aimed to: (1) provide insight into the genetic pathogenesis of SUI by gathering and synthesizing the available data from studies evaluating differential gene expression in SUI patients and (2) identify possible novel therapeutic targets and leads.
A systematic literature search was conducted through September 2017 for the concepts of genetics and SUI. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in SUI were performed using GeneMANIA software.
Of 3019 studies, 4 were included in the final analysis. A total of 13 genes were identified as being differentially expressed in SUI patients. Eleven genes were overexpressed: skin-derived antileukoproteinase (SKALP/elafin), collagen type XVII alpha 1 chain (COL17A1), plakophilin 1 (PKP1), keratin 16 (KRT16), decorin (DCN), biglycan (BGN), protein bicaudal D homolog 2 (BICD2), growth factor receptor-bound protein 2 (GRB2), signal transducer and activator of transcription 3 (STAT3), apolipoprotein E (APOE), and Golgi SNAP receptor complex member 1 (GOSR1), while two genes were underexpressed: fibromodulin (FMOD) and glucocerebrosidase (GBA). GeneMANIA revealed that these genes are involved in intermediate filament cytoskeleton and extracellular matrix organization.
Many genes are involved in the pathogenesis of SUI. Furthermore, whole-genome studies are warranted to identify these genetic connections. This study lays the groundwork for future research and the development of novel therapies and SUI biomarkers in clinical practice.
International urogynecology journal. 2019 Jul 16 [Epub ahead of print]
Ilaha Isali, Amr Mahran, Ahmad O Khalifa, David Sheyn, Mandy Neudecker, Arshna Qureshi, Britt Conroy, Fredrick R Schumacher, Adonis K Hijaz, Sherif A El-Nashar
Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Core Library, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Department of Anesthesiology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Family Medicine, Metro Health Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. .