{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:08:32Z","timestamp":1788343712035,"version":"build-2803163510"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Marcel Waldinger Foundation","award":["E.20.31.017"],"award-info":[{"award-number":["E.20.31.017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>In this study we sought to evaluate the genetic association between the rs6296 polymorphism of the 5-HT1b receptor and intravaginal ejaculation latency times (IELTs) in men with LPE compared with men in a control group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study was a prospective observational genetic case-control association study. The LPE definition of the International Society for Sexual Medicine (ISSM) 2013 was used. Patients were recruited in 2005-2009 while attending the department of Neurosexology, HagaZiekenhuis, the Netherlands. We obtained IELTs with the stopwatch method. Polymerase chain reaction (PCR) was used for genotyping rs6296. A randomly selected group of European Caucasian men from the 1000GENOMES project was used as a control group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>Study outcomes included results of comparisons of analysis of variance (ANOVA) tests between genotypes and IELTs in study participants, genotypes of cases and controls determined with the chi-square test, and expressions of allelotype- and genotype-specific risks for LPE determined with odds ratios.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 67 men with LPE were included in this study. The geometric mean (SD) IELT was 32.0\u00a0(27.4) seconds and was non-normally distributed. Genotype frequencies consisted of 29 (43.3%) GG, 31 (46.3%) GC, and 7(10.4%) CC individuals in the LPE group. Log-transformed IELTs were not statistically significant (per ANOVA tests) in men with GG, GC, or CC genotypes (P\u2009=\u2009.54). Genotype frequencies consisted of 16 (6.6%) GG; 93 (38.8%) GC, and 131 (54.6%) CC individuals in the control group (n\u2009=\u2009240). Significant differences were found when comparing allele (P\u2009=\u20091.02e-17) and genotype (P\u2009=\u20093.22e-16) frequencies in cases and controls using a chi-square test. A statistically significant increased risk for LPE was found for carriers of the G allele (OR 5.62; 95% CI 4.13-9.42). Statistically significant risks were also found for the CG genotype (OR 6.24; 95% CI 2.63-14.77) and the GG genotype (OR 33.92; 95% CI 12.79-89.93).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical implications<\/jats:title>\n                  <jats:p>By investigating polymorphisms in target genes the neuro-pathophysiology of LPE could be further elaborated, potentially leading to more effective treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths and limitations<\/jats:title>\n                  <jats:p>This is to our knowledge the first study investigating rs6296 with regard to LPE. By using a strict definition for LPE (ISSM 2013) and using the stopwatch method for measuring IELTs, bias in selection of true LPE patients will be relatively low. This study is limited by a relatively small study population and the lack of IELT data in the control group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study shows a genetic association in rs6296 in men with LPE compared with healthy controls. This result warrants attempted replication in future studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdad159","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T06:05:57Z","timestamp":1701756357000},"page":"122-128","source":"Crossref","is-referenced-by-count":2,"title":["The rs6296 polymorphism in the 5-HT1b receptor in Dutch men with lifelong premature ejaculation: a genetic case-control association study"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0940-4840","authenticated-orcid":false,"given":"Joost J","family":"van Raaij","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, VieCuri Medical Centre , Tegelseweg 210, 5912 BL Venlo , The Netherlands"},{"name":"Department of Clinical Pharmacy and Toxicology, MUMC+ , P. 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