{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:31:14Z","timestamp":1784914274261,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high\u2010risk cardiovascular disease patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (<jats:italic>n<\/jats:italic>\u00a0=\u00a0112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T\u2010786C), genotyped by fluorescence polarization assays, were registered. The 27\u2010bp variable number of the tandem repeat polymorphism in intron 4 (intron4b\/a) was analyzed by polymerase chain reaction\u2010restriction fragment length polymorphism. Association analyses were run with the R\u20103.2.0 software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant association between endothelial nitric oxide synthase 786\u2010TT (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.005) and the aa\/ac of intron 4 variable number of the tandem repeat (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60\u00a0\u00b1\u00a09 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3\u2010months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50\u00a0\u00b1\u00a016 scores, the International Index of Erectile Function\u2010Erectile Function 21\u00a0\u00b1\u00a010 scores, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55\u00a0\u00b1\u00a023 scores, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894\u2010T allele (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high\u2010risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13671","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:54:46Z","timestamp":1719824086000},"page":"794-803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Erectile dysfunction in cardiovascular patients: A prospective study of the <i>eNOS<\/i> gene T\u2010786C, G894T, and INTRON variable number of the tandem repeat functional interaction"],"prefix":"10.1111","volume":"13","author":[{"given":"Ana","family":"Segura","sequence":"first","affiliation":[{"name":"Urology Department, Andrology Unit Dr. Balmis General University Hospital  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Muriel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Pharmacogenetic Unit Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Mir\u00f3","sequence":"additional","affiliation":[{"name":"Department of Applied Statistics and Operational Research, and Quality Universitat Politecnica de Val\u00e8ncia, Campus of Alcoi Plaza Ferrandiz y Carbonell s\/n  Alcoy Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Agull\u00f3","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Pharmacogenetic Unit Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Arrarte","sequence":"additional","affiliation":[{"name":"Cardiology Department Dr. Balmis General University Hospital  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Carracedo","sequence":"additional","affiliation":[{"name":"Department of Statistics and Applied Operational Research and Quality Universitat Polit\u00e8cnica de Val\u00e8ncia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Zandonai","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Pharmacogenetic Unit Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"},{"name":"Department of Psychology of Developmental and Socialization Processes \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Peir\u00f3","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Pharmacogenetic Unit Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"},{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit Institute of Bioengineering Miguel Hern\u00e1ndez University Avda. de la Universidad s\/n  Elche Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10102221"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.74.Suppl_3.S30"},{"key":"e_1_2_12_4_1","first-page":"203","article-title":"Erectile dysfunction: a sentinel symptom?","volume":"15","author":"Osta P","year":"2005","journal-title":"Prog En Urol"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67900-1"},{"key":"e_1_2_12_6_1","first-page":"101","article-title":"Prevalence of erectile dysfunction in Spanish primary care setting and its association with cardiovascular risk factors and cardiovascular diseases. SIMETAP\u2010ED study","volume":"31","author":"Ruiz\u2010Garc\u00eda A","year":"2019","journal-title":"Clin Investig Arterioscler"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2006.01274.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-023-00632-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11573"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2020.1849135"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.602532"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102370"},{"key":"e_1_2_12_13_1","first-page":"153","article-title":"Endothelial nitric oxide synthase (eNOS) and the cardiovascular system: in physiology and in disease states","volume":"15","author":"Tran N","year":"2022","journal-title":"Am J Biomed Sci Res"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.4065\/82.10.1203"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.07.008"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.6.2832"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2009.01226.x"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.931887"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4933-5-4"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2011.02638.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.22.2864"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.8.12.1723"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3132\/dvdr.2008.018"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000238124.91161.02"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900857"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2005.00119.x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sxmr.2018.01.001"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2015.992722"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13010108"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.12.107"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00593-6"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12200"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.15313"},{"key":"e_1_2_12_34_1","first-page":"698","article-title":"Erectile dysfunction as a sentinel marker of endothelial dysfunction disease","volume":"50","author":"Lojanapiwat B","year":"2009","journal-title":"Singapore Med J"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aju.2013.03.003"},{"key":"e_1_2_12_36_1","first-page":"1100","article-title":"Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk","volume":"90","author":"Buranakitjaroen P","year":"2007","journal-title":"J Med Assoc Thail"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2001.tb11009.x"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2013.10.013"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12543"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20010187"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8267"},{"key":"e_1_2_12_42_1","first-page":"90","article-title":"The combined ratios of L\u2010arginine and asymmetric and symmetric dimethylarginine as biomarkers in spontaneously hypertensive rats","volume":"159","author":"Hsu C\u2010N","year":"2012","journal-title":"Transl Res J Lab Clin Med"},{"key":"e_1_2_12_43_1","first-page":"15270","article-title":"Promoter polymorphism T\u2010786C, 894G\u2192T at exon 7 of endothelial nitric oxide synthase gene are associated with risk of osteoporosis in Sichuan region male residents","volume":"8","author":"Gu Z","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.December.9.23"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2579626"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02588.x"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.163300"},{"key":"e_1_2_12_48_1","first-page":"639","article-title":"Lymphomatoid granulomatosis. Value of standard radiography. Apropos of a case","volume":"64","author":"Marsot\u2010Dupuch K","year":"1983","journal-title":"J Radiol"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2005.00165.x"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2009.06.063"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00169-8"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2005.05.049"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2003.10.032"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-015-0540-9"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2018.04.012"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2016.01083"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-019-01945-w"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018583"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.13671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T13:24:43Z","timestamp":1748352283000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.13671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/andr.13671"],"URL":"https:\/\/doi.org\/10.1111\/andr.13671","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2023-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}