{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:02:35Z","timestamp":1760148155381,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Stress urinary incontinence (SUI) is defined as unintentional urine leakage occurring as a consequence of increased intraabdominal pressure due to absent or weak musculus detrusor contractility. It affects postmenopausal women more often than premenopausal and is associated with quality of life (QoL) deterioration. The complex SUI etiology is generally perceived as multifactorial; however, the overall impact of environmental and genetic influences is deficiently understood. In this research report, we have disclosed the upregulation of 15 genes and the downregulation of 2 genes in the genetic etiology of SUI according to the accessible scientific literature. The analytical methods used for the analysis of gene expression in the studies investigated were immunohistochemistry, immunofluorescence staining, PCR, and Western blot. In order to facilitate the interpretation of the results, we have used GeneMania, a potent software which describes genetic expression, co-expression, co-localization, and protein domain similarity. The importance of this review on the genetic pathophysiology of SUI lies in determining susceptibility for targeted genetic therapy, detecting clinical biomarkers, and other possible therapeutic advances. The prevention of SUI with the timely recognition of genetic factors may be important for avoiding invasive operative urogynecological methods.<\/jats:p>","DOI":"10.3390\/medicina59040700","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T02:30:15Z","timestamp":1680575415000},"page":"700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Gene Expression in Stress Urinary Incontinence: An Integrative Review of Evidence"],"prefix":"10.3390","volume":"59","author":[{"given":"Iva","family":"Mili\u010di\u0107","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Centre, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-8704","authenticated-orcid":false,"given":"Mislav","family":"Miku\u0161","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Centre, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Vrbani\u0107","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Centre, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5729-7664","authenticated-orcid":false,"given":"Dr\u017eislav","family":"Kalafati\u0107","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Centre, 10 000 Zagreb, Croatia"},{"name":"Medical School, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0090-4295(02)02243-4","article-title":"The Standardisation of Terminology in Lower Urinary Tract Function: Report from the Standardisation Sub-Committee of the International Continence Society","volume":"61","author":"Abrams","year":"2003","journal-title":"Urology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/ijgo.12232","article-title":"A Meta-Analysis of Pelvic Floor Muscle Training for the Treatment of Urinary Incontinence","volume":"138","author":"Nie","year":"2017","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/nau.22657","article-title":"ICIQ Symptom and Quality of Life Instruments Measure Clinically Relevant Improvements in Women with Stress Urinary Incontinence: ICIQ-UI SF and ICIQ-LUTSqol Correlation to PGI-I","volume":"34","author":"Stenlund","year":"2015","journal-title":"Neurourol. Urodynam."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00404-019-05371-x","article-title":"Treatment of Urinary Incontinence in Overweight Women by a Multidisciplinary Lifestyle Intervention","volume":"301","author":"Andreasen","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1464-410X.2003.04609.x","article-title":"The Prevalence of Urinary Incontinence in Women in Four European Countries","volume":"93","author":"Hunskaar","year":"2004","journal-title":"BJU Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s13063-015-0803-1","article-title":"Magnetic Stimulation for Stress Urinary Incontinence: Study Protocol for a Randomized Controlled Trial","volume":"16","author":"Lim","year":"2015","journal-title":"Trials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e15572","DOI":"10.1097\/MD.0000000000015572","article-title":"Magnetic Stimulation for Female Patients with Stress Urinary Incontinence, a Meta-Analysis of Studies with Short-Term Follow-Up","volume":"98","author":"Peng","year":"2019","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.maturitas.2005.09.004","article-title":"Medical Resource Utilisation and Cost of Care for Women Seeking Treatment for Urinary Incontinence in an Outpatient Setting","volume":"52","author":"Papanicolaou","year":"2005","journal-title":"Maturitas"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/S0002-9378(12)91840-2","article-title":"Structural Support of the Urethra as It Relates to Stress Urinary Incontinence: The Hammock Hypothesis","volume":"170","author":"DeLancey","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1046\/j.1471-0528.2003.02327.x","article-title":"Are Smoking and Other Lifestyle Factors Associated with Female Urinary Incontinence? The Norwegian EPINCONT Study","volume":"110","author":"Hannestad","year":"2003","journal-title":"BJOG"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0090-4295(90)80211-5","article-title":"Medical Correlates of Urinary Incontinence in the Elderly","volume":"36","author":"Diokno","year":"1990","journal-title":"Urology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1136\/bmj.329.7471.889","article-title":"Familial Risk of Urinary Incontinence in Women: Population Based Cross Sectional Study","volume":"329","author":"Hannestad","year":"2004","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S0002-9378(96)70437-4","article-title":"Female Urinary Stress Incontinence--Does It Have Familial Prevalence?","volume":"174","author":"Mushkat","year":"1996","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1067\/mob.2002.124842","article-title":"Familial Incidence of Urinary Incontinence","volume":"187","author":"Elia","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.eururo.2007.12.004","article-title":"Genetic Influence on Stress Urinary Incontinence and Pelvic Organ Prolapse","volume":"54","author":"Altman","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/MOU.0b013e32833a4436","article-title":"Genetic Influences on Stress Urinary Incontinence","volume":"20","author":"McKenzie","year":"2010","journal-title":"Curr. Opin. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s00192-010-1222-1","article-title":"Microarray Analysis of Differentially Expressed Genes in Vaginal Tissues in Postmenopausal Women. The Role of Stress Urinary Incontinence","volume":"21","author":"Tong","year":"2010","journal-title":"Int. Urogynecol J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lo, C.K.-L., Mertz, D., and Loeb, M. (2014). Newcastle-Ottawa Scale: Comparing Reviewers\u2019 to Authors\u2019 Assessments. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-45"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/humrep\/dei276","article-title":"Microarray Analysis of Differentially Expressed Genes in Vaginal Tissues from Women with Stress Urinary Incontinence Compared with Asymptomatic Women","volume":"21","author":"Chen","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1093\/humrep\/dem039","article-title":"Differences in MRNA and Protein Expression of Small Proteoglycans in Vaginal Wall Tissue from Women with and without Stress Urinary Incontinence","volume":"22","author":"Wen","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1097\/GME.0000000000000222","article-title":"Differential Expression of MicroRNAs in Periurethral Vaginal Wall Tissues of Postmenopausal Women with and without Stress Urinary Incontinence","volume":"21","author":"Liu","year":"2014","journal-title":"Menopause"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"F394","DOI":"10.1152\/ajprenal.00174.2020","article-title":"ANO1 in Urethral SMCs Contributes to Sex Differences in Urethral Spontaneous Tone","volume":"319","author":"Chen","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/JU.0000000000001822","article-title":"Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence","volume":"206","author":"Cartwright","year":"2021","journal-title":"J. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.jpedsurg.2020.02.001","article-title":"Altered Anoctamin-1 and Tyrosine Phosphorylation in Congenital Ureteropelvic Junction Obstruction","volume":"55","author":"Hunziker","year":"2020","journal-title":"J. Pediatr. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.pathol.2018.11.002","article-title":"Apolipoprotein E in Lipoprotein Metabolism, Health and Cardiovascular Disease","volume":"51","author":"Marais","year":"2019","journal-title":"Pathology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fncel.2018.00142","article-title":"Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-\u039aB Signaling Pathway","volume":"12","author":"Yang","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1111\/febs.14791","article-title":"Breaking down Chronic Inflammatory Diseases: The Role of Biglycan in Promoting a Switch between Inflammation and Autophagy","volume":"286","author":"Roedig","year":"2019","journal-title":"FEBS J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/03008207.2019.1669577","article-title":"Evidence of Biglycan Structure-Function in Bone Homeostasis and Aging","volume":"61","author":"Miguez","year":"2020","journal-title":"Connect. Tissue Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ajhg.2013.04.018","article-title":"Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia","volume":"92","author":"Oates","year":"2013","journal-title":"Am. J. Human. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1080\/21678421.2017.1304557","article-title":"A Novel Mutation of BICD2 Gene Associated with Juvenile Amyotrophic Lateral Sclerosis","volume":"18","author":"Huang","year":"2017","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/humu.22764","article-title":"Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)","volume":"36","author":"Jonsson","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8868245","DOI":"10.1155\/2020\/8868245","article-title":"High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-\u039aB Pathway in Pancreatic Adenocarcinoma","volume":"2020","author":"Mao","year":"2020","journal-title":"J. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.matbio.2017.10.005","article-title":"Decorin Is a Devouring Proteoglycan: Remodeling of Intracellular Catabolism via Autophagy and Mitophagy","volume":"75\u201376","author":"Buraschi","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.sbi.2012.07.012","article-title":"The Galactosaminoglycan-Containing Decorin and Its Impact on Diseases","volume":"22","author":"Seidler","year":"2012","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.biocel.2010.10.009","article-title":"Endothelin-1: Physiological and Pathological Roles in Myometrium","volume":"43","author":"Tanfin","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.biocel.2008.01.022","article-title":"The Endothelin Axis in Cancer","volume":"40","author":"Bagnato","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_38","unstructured":"Andersson, K.E., and Michel, M.C. (2011). Handbook of Experimental Pharmacology, Springer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1046\/j.1464-410x.1999.00248.x","article-title":"Up-Regulation of Endothelin-B (ETB) Receptors and ETB Receptor-Mediated Rabbit Detrusor Contraction in Partial Bladder Outlet Obstruction: PARTIAL BLADDER OUTLET OBSTRUCTION","volume":"84","author":"Khan","year":"2001","journal-title":"BJU Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ejphar.2007.11.021","article-title":"In Vitro and in Vivo Effects of Endothelin-1 and YM598, a Selective Endothelin ETA Receptor Antagonist, on the Lower Urinary Tract","volume":"580","author":"Ukai","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.urology.2007.10.025","article-title":"Therapeutic Effects of Endothelin-A Receptor Antagonist on Bladder Overactivity in Rats with Chronic Spinal Cord Injury","volume":"71","author":"Ogawa","year":"2008","journal-title":"Urology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0092-8674(00)80191-9","article-title":"Protein Interactions Regulating Vesicle Transport between the Endoplasmic Reticulum and Golgi Apparatus in Mammalian Cells","volume":"89","author":"Hay","year":"1997","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lewis, T.R., Smith, J., Griffin, K., Aguiar, S., Rueb, K.F., Holmberg-Douglas, N., Sampson, E.M., Tomasetti, S., Rodriguez, S., and Stachura, D.L. (2020). NHD2-15, a Novel Antagonist of Growth Factor Receptor-Bound Protein-2 (GRB2), Inhibits Leukemic Proliferation. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236839"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1139\/bcb-2014-0001","article-title":"Interaction of Grb2 SH3 Domain with UVRAG in an Alzheimer\u2019s Disease\u2013like Scenario","volume":"92","author":"Roy","year":"2014","journal-title":"Biochem. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yin, M., and Zhang, L. (2019). Keratin 6, 16 and 17\u2014Critical Barrier Alarmin Molecules in Skin Wounds and Psoriasis. Cells, 8.","DOI":"10.3390\/cells8080807"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1083\/jcb.150.4.921","article-title":"Introducing a Null Mutation in the Mouse K6\u03b1 and K6\u03b2 Genes Reveals Their Essential Structural Role in the Oral Mucosa","volume":"150","author":"Wong","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hirano, S., and Kanno, S. (2015). Macrophage Receptor with Collagenous Structure (MARCO) Is Processed by Either Macropinocytosis or Endocytosis-Autophagy Pathway. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142062"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"666423","DOI":"10.3389\/fped.2021.666423","article-title":"Macrophage Receptor With Collagenous Structure Polymorphism and Recurrent Respiratory Infections and Wheezing During Infancy: A 5-Years Follow-Up Study","volume":"9","author":"Savino","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1007\/s00018-019-03083-8","article-title":"Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering","volume":"76","author":"Fuchs","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-2230.2004.01467.x","article-title":"Plakophilin 1: An important stabilizer of desmosomes","volume":"29","author":"South","year":"2004","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00192-019-04025-5","article-title":"Gene expression in stress urinary incontinence: A systematic review","volume":"31","author":"Isali","year":"2020","journal-title":"Int. Urogynecol. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9567","DOI":"10.1007\/s13277-015-3628-3","article-title":"Plakophilin 1-deficient cells upregulate SPOCK1: Implications for prostate cancer progression","volume":"36","author":"Yang","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1399-0004.1998.tb03703.x","article-title":"SKALP\/elafin gene polymorphisms are not associated with pustular forms of psoriasis","volume":"54","author":"Kuijpers","year":"1998","journal-title":"Clin. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s004030100238","article-title":"Development and application of monoclonal antibodies against SKALP\/elafin and other trappin family members","volume":"293","author":"Vandermeeren","year":"2001","journal-title":"Arch Derm. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-020-01258-7","article-title":"Targeting STAT3 in Cancer Immunotherapy","volume":"19","author":"Zou","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/humu.20676","article-title":"Gaucher disease: Mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA)","volume":"29","author":"Hruska","year":"2008","journal-title":"Hum. Mutat."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/4\/700\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:09:11Z","timestamp":1760123351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/4\/700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,3]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["medicina59040700"],"URL":"https:\/\/doi.org\/10.3390\/medicina59040700","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2023,4,3]]}}}