title: Are single nucleotide polymorphisms in the oxytocin and vasopressin 1A/1B receptor genes likely candidates for variation in ejaculatory function?
abstract: What's known on the subject? and What does the study add? There is also evidence that the etiology of premature ejaculation is partially genetic. So far, all molecular genetic studies of premature ejaculation have focused on serotonergic and dopaminergic genes. Serotonergic and dopaminergic neurotransmission aside, studies on both animals and humans have shown that both oxytocin and vasopressin are also involved in ejaculatory function. The present study is, to our knowledge, the first to investigate effects of polymorphisms in oxytocin and vasopressin receptor genes on ejaculatory function. Although a large sample (1517 men) was available for the present study, we could not detect any clear-cut effects of any gene variant on ejaculatory function. We detected a heterozygote effect of one polymorphism (rs75775) in the oxytocin receptor gene. Rare variants of the vasopressin receptor 1A gene may theoretically have a stronger impact on ejaculatory function, but would need a very large sample in order to be established. Based on our results, we conclude that the oxytocin and vasopressin receptor genes are unlikely targets for successful pharmacogenetic interventions.
  
  
  OBJECTIVE
  • To investigate associations between single nucleotide polymorphisms (SNPs) linked to the oxytocin, and arginine vasopressin 1A and 1B receptor genes and ejaculatory function. • To investigate these associations in a large, population-based sample.
  
  
  METHODS
  • In all, 1517 male twins and non-twin brothers of twins aged 18-45 years (mean = 26.43; sd = 4.87) provided questionnaire data regarding ejaculatory function and relevant covariates and saliva samples for genotyping. • A Bayesian linear mixed-effects model, which appropriately controls for between-subjects dependence, was used to estimate genotype associations. • We corrected for multiple testing using a linkage disequilibrium correlation measure.
  
  
  RESULTS
  • We found a heterozygote effect on one SNP in the oxytocin receptor gene (rs75775), so that individuals heterozygous for this SNP had significantly elevated risk for premature ejaculation symptoms compared with carriers of either homozygote. • Several SNPs in the arginine vasopressin receptor genes had rare or very rare genotypes. This study may be underpowered to detect potential effects of rare genotypic variants in arginine vasopressin receptor genes.
  
  
  CONCLUSIONS
  • Our results regarding the oxytocin receptor polymorphisms support previous studies that indicate a complex relationship between oxytocin and ejaculatory function. • Oxytocin receptor genes are, for example, unlikely suitable targets for pharmacogenetic intervention studies. • Rare variants in arginine vasopressin receptor genes may have significant effects on premature ejaculation, but would need larger sample sizes or case-control designs to be detected.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden. pjern@abo.fi
authors.forename: Patrick
authors.initials: P
authors.lastname: Jern
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Ada
authors.initials: A
authors.lastname: Johansson
authors.forename: Lina
authors.initials: L
authors.lastname: Jonsson
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.forename: N Kenneth
authors.initials: NK
authors.lastname: Sandnabba
authors.forename: Pekka
authors.initials: P
authors.lastname: Santtila
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D004247:DNA / Q000235:genetics*; D004542:Ejaculation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D061686:Premature Ejaculation / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017483:Receptors, Vasopressin; D010121:Oxytocin; D004247:DNA