Preliminary evidence for an association between variants of the catechol-o-methyltransferase (COMT) gene and premature ejaculation

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Patrick Jern, Ada Johansson, Jana Strohmaier, Jens Treutlein, Juhana Piha, Marcella Rietschel
Publisher: Elsevier
Publication year: 2017
Journal: The Journal of Sexual Medicine
Journal acronym: J Sex Med
Volume number: 14
Issue number: 12
Start page: 1558
End page: 1565


Background. Studies have suggested that dopamine plays a role in
the neurobiological mechanism that triggers ejaculation, leading scientists to
hypothesize that dopamine-related genetic polymorphisms may contribute to
symptoms of premature ejaculation (PE).

Aim. To investigate associations between dopamine receptor- and
catechol-O-methyltransferase (COMT, an enzyme involved in the catabolization of
dopamine) gene-linked polymorphisms and PE.

Methods. PE status in the patient groups was determined by clinical diagnosis
performed by a physician specializing in sexual medicine. Self-reported PE
symptoms from a validated questionnaire were also reported. We collected saliva
samples from 149 PE patients and from 1,022 controls from a population-based
sample. In total, we tested associations between PE and 11 single nucleotide
polymorphisms in the dopamine receptor D1, D2, and D3 genes, and in the COMT

Outcomes. We found no associations between dopamine receptor
gene polymorphisms and PE, but two COMT-linked
loci (rs4680 and rs4818) had significant associations after correction for
multiple testing.

Results. One of the COMT-gene-linked
loci that was associated with PE symptoms in the present study, rs4680, is a
well-documented functional polymorphism, which causes a valine-to-methionine
substitution. The other polymorphism, rs4818, is in high linkage disequilibrium
with the rs4680 locus, indicating that they capture the same effect.
Surprisingly, the rs4680 variant that was statistically significantly more
prevalent in the PE patient group (i.e., the valine-encoding allele) has
previously been associated with higher enzymatic activity, and therefore lower
synaptic dopamine levels.

Clinical Translation. Drugs targeting the dopaminergic system may affect PE

Strengths & Limitations. No replication sample was available for the present
study, thus our findings should be interpreted with caution. Moreover, a
limitation of our study is the small sample size in the context of genetic
association studies (although it should be mentioned, that genetically
informative samples with phenotypic information about PE symptoms are scarce,
and most previous genetic association studies of PE have employed samples or
similar or smaller size). However, our results are plausible: we report an
association between one of the most extensively studied and understood genetic
polymorphisms in psychiatric research and PE, and our results are in line with
the long-standing hypothesis that dopamine influences human ejaculatory

Conclusions. We report an association between two COMT gene-linked loci and PE symptoms,
but our results should be treated with caution until independently replicated.

Last updated on 2020-14-08 at 04:15