{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:52:48Z","timestamp":1789419168907,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erectile dysfunction (ED) is a significant disorder commonly found in patients with cardiovascular diseases and diabetes mellitus. Recent updates have indicated that statins may also contribute to an increased risk of ED. This cross-sectional genetic study involved 246 cardiac patients attending normal visits at Hospital Universiti Sains Malaysia (USM) Kubang Kerian outpatient clinics. The patients were categorized into four groups: statins with ED (group 1), statins without ED (group 2), diabetes with statin without ED (group 3), and healthy patients without diabetes mellitus and statin use (group 4). Six genes were hypothesized to influence ED: CYP19A1, CYP17A1, SIM1, TP53, NR2F2, and NOS3, with different polymorphisms and variants investigated in this study. Overall, statin therapy was found to have a negative impact on ED by affecting NR2F2-AS1 and NOS3. However, atorvastatin showed varying effects on ED for all genes, with the highest impact observed with CYP17A1 and the lowest with CYP19A1. In conclusion, this study revealed novel findings related to genetic factors influencing ED in Malaysian males during statin use.<\/jats:p>","DOI":"10.3390\/ijms26178447","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Prediction of Erectile Dysfunction Caused by Statins Among Malaysian Cardiac Patients"],"prefix":"10.3390","volume":"26","author":[{"given":"Naam Bahjat Ahmed","family":"Adeeb","sequence":"first","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"},{"name":"College of Medicine, Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad 79G3+3RR, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2683-6207","authenticated-orcid":false,"given":"Hadeer Akram","family":"Al-Ani","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-9468","authenticated-orcid":false,"given":"Nur Aizati Athirah","family":"Daud","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"},{"name":"School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-4707","authenticated-orcid":false,"given":"Ruzilawati","family":"Abu Bakar","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0826-4724","authenticated-orcid":false,"given":"Imran","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0161-8203","authenticated-orcid":false,"given":"Dzul Azri Mohamed","family":"Noor","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilfalil","family":"Bin Alwi","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, L., Huang, D.-D., Li, Y., Ma, C.-C., Shi, M., Su, B.-X., and Shi, G.-J. (2019). Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomed. Pharmacother., 112.","DOI":"10.1016\/j.biopha.2019.01.046"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.11622\/smedj.2018049","article-title":"Prevalence and predictors of erectile dysfunction in adult male outpatient clinic attendees in Johor, Malaysia","volume":"60","author":"Nordin","year":"2019","journal-title":"Singap. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.tox.2016.06.015","article-title":"Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model","volume":"359-360","author":"Abdallah","year":"2016","journal-title":"Toxicology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41569-018-0098-5","article-title":"Safety and efficacy of statin therapy","volume":"15","author":"Adhyaru","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/BJMMR\/2017\/31150","article-title":"The Effect of Two Types of Statins (Rosuvastatin and Atorvastatin) on the Fertility of Male and Female Mice","volume":"19","author":"Bustan","year":"2017","journal-title":"Br. J. Med. Med. Res."},{"key":"ref_6","first-page":"1","article-title":"Statins and Erectile Dysfunction","volume":"37","author":"Kostis","year":"2019","journal-title":"Korean Soc. Sex. Med. Androl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12995","DOI":"10.1111\/and.12995","article-title":"Semen parameters are unaffected by statin use in men evaluated for infertility","volume":"50","author":"Keihani","year":"2018","journal-title":"Andrologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1159\/000457881","article-title":"Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR","volume":"41","author":"Cui","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ijcard.2017.01.141","article-title":"Association between statins use and erectile dysfunction","volume":"239","author":"Zhao","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s12020-019-02008-6","article-title":"Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene","volume":"65","author":"Aguirre","year":"2019","journal-title":"Endocrine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Roosenboom, J., Indencleef, K., Lee, M.K., Hoskens, H., White, J.D., Liu, D., Hecht, J.T., Wehby, G.L., Moreno, L.M., and Hodges-Simeon, C. (2018). SNPs Associated With Testosterone Levels Influence Human Facial Morphology. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00497"},{"key":"ref_12","unstructured":"NCBI (2025, June 15). CYP19A1 Cytochrome P450 Family 19 Subfamily A Member 1 [Homo Sapiens (Human)]. National Center for Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/1588."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.111.094714","article-title":"Simvastatin Reduces Steroidogenesis by Inhibiting Cyp17a1 Gene Expression in Rat Ovarian Theca-Interstitial Cells","volume":"86","author":"Ortega","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_14","unstructured":"NCBI (2025, June 15). CYP17A1 Cytochrome P450 Family 17 Subfamily A Member 1 [Homo Sapiens (Human)]. National Center for Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/1586."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11018","DOI":"10.1073\/pnas.1809872115","article-title":"Genetic variation in the SIM1 locus is associated with erectile dysfunction","volume":"115","author":"Jorgenson","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/jmcb\/mjs064","article-title":"A new role of p53 in regulating lipid metabolism","volume":"5","author":"Wang","year":"2013","journal-title":"J. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wankanit, S., Zidoune, H., Bignon-Topalovic, J., Schlick, L., Houzelstein, D., Fus\u00e9e, L., Boukri, A., Nouri, N., McElreavey, K., and Bashamboo, A. (2024). Evidence for NR2F2\/COUP-TFII involvement in human testis development. Sci. Rep., 17869.","DOI":"10.1101\/2024.01.05.574424"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ijsu.2018.04.012","article-title":"Endothelial nitric oxide synthase gene polymorphisms and risk of erectile dysfunction: An updated meta-analysis of genetic association studies","volume":"54","author":"Yao","year":"2018","journal-title":"Int. J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111261","DOI":"10.1016\/j.mce.2021.111261","article-title":"Steroidogenic cytochrome P450 17A1 structure and function","volume":"528","author":"Scott","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4103\/aja202335","article-title":"Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic","volume":"26","author":"Bai","year":"2024","journal-title":"Asian J. Androl."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ferezin, L.P., Kayzuka, C., Pereira, V.C.R., de Andrade, M.F., Molina, C.A.F., Tucci, S., Tanus-Santos, J.E., and Lacchini, R. (2023). The rs2682826 Polymorphism of the NOS1 Gene Is Associated with the Degree of Disability of Erectile Dysfunction. Life, 13.","DOI":"10.3390\/life13051082"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Su, Q., Wang, R., Luo, Y., Tang, Q., and Wang, K. (2024). Genetic association of lipid-lowering drug target genes with erectile dysfunction and male reproductive health. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1362499"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yuan, P., Chen, Y., Sun, T., Cui, L., Wei, Y., Li, T., and Meng, Q. (2023). Exploring potential genes and mechanisms linking erectile dysfunction and depression. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1221043"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.gene.2015.09.061","article-title":"Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms","volume":"575","author":"Lacchini","year":"2016","journal-title":"Gene"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hattori, A., and Fukami, M. (2023). Nuclear Receptor Gene Variants Underlying Disorders\/Differences of Sex Development through Abnormal Testicular Development. Biomolecules, 13.","DOI":"10.3390\/biom13040691"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kataoka, T., Hotta, Y., and Kimura, K. (2023). A review of experimental techniques for erectile function researches and development of medical technology using animal erectile dysfunction models in sexual and reproductive medicine. Reprod. Med. Biol., 22.","DOI":"10.1002\/rmb2.12513"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1007\/s00380-021-01872-5","article-title":"Association between testosterone and lipid profiles under statin therapy and its clinical impact on the cardiovascular event risk","volume":"36","author":"Nakayama","year":"2021","journal-title":"Heart Vessels."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.diabres.2016.07.026","article-title":"Rosuvastatin decreases free testosterone levels but does not influence sexual function in men with type 2 diabetes","volume":"120","author":"Hsieh","year":"2016","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.sxmr.2020.02.001","article-title":"Gene Polymorphisms Affecting Erectile Dysfunction","volume":"8","author":"Mostafa","year":"2020","journal-title":"Sex. Med. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2036337","DOI":"10.1001\/jamanetworkopen.2020.36337","article-title":"Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis","volume":"4","author":"Mykoniatis","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e14408","DOI":"10.1111\/and.14408","article-title":"Impact of atorvastatin on erectile dysfunction: A meta-analysis and systematic review","volume":"54","author":"Su","year":"2022","journal-title":"Andrologia"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Omolaoye, T.S., Halabi, M.O., Mubarak, M., Cyril, A.C., Duvuru, R., Radhakrishnan, R., and Du Plessis, S.S. (2022). Statins and Male Fertility: Is There a Cause for Concern?. Toxics, 10.","DOI":"10.3390\/toxics10100627"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pons-Rejraji, H., Brugnon, F., Sion, B., Maqdasy, S., Gouby, G., Pereira, B., Marceau, G., Gremeau, A.-S., Drevet, J., and Grizard, G. (2014). Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: A pilot prospective clinical trial. Reprod. Biol. Endocrinol., 12.","DOI":"10.1186\/1477-7827-12-65"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.52586\/4926","article-title":"Regulation of NOS expression in vascular diseases","volume":"26","author":"Pautz","year":"2021","journal-title":"Front. Biosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1139\/cjpp-2017-0113","article-title":"TNF-\u03b1 antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats","volume":"96","author":"Yazir","year":"2018","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Freudenstein, D., Litchfield, C., Caramia, F., Wright, G., Solomon, B.J., Ball, D., Keam, S.P., Neeson, P., Haupt, Y., and Haupt, S. (2020). TP53 Status, Patient Sex, and the Immune Response as Determinants of Lung Cancer Patient Survival. Cancers, 12.","DOI":"10.3390\/cancers12061535"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1200\/JCO.2024.42.4_suppl.82","article-title":"Impact of TP53, RB1, and PTEN mutations on overall survival in metastatic prostate cancer: A multi-center study via the Guardian Research Network","volume":"42","author":"Ganiyani","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_38","first-page":"464","article-title":"Treatment with statins and testosterone levels in men","volume":"65","author":"Kubicka","year":"2014","journal-title":"Endokrynol. Polska"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.4103\/jfmpc.jfmpc_1871_20","article-title":"Prevalence of erectile dysfunction and associated factors among males visiting family medicine clinics in a Tertiary Care Hospital in Karachi, Pakistan","volume":"10","author":"Saeed","year":"2021","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/sj.ijir.3900902","article-title":"Reliability and validity of the Malay version of the International Index of Erectile Function (IIEF-15) in the Malaysian population","volume":"14","author":"Quek","year":"2002","journal-title":"Int. J. Impot. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:54Z","timestamp":1760034954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,30]]},"references-count":40,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178447"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178447","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,30]]}}}