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

Background. Studies have suggested that dopamine plays a role inthe neurobiological mechanism that triggers ejaculation, leading scientists tohypothesize that dopamine-related genetic polymorphisms may contribute tosymptoms of premature ejaculation (PE).

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

Methods. PE status in the patient groups was determined by clinical diagnosisperformed by a physician specializing in sexual medicine. Self-reported PEsymptoms from a validated questionnaire were also reported. We collected salivasamples from 149 PE patients and from 1,022 controls from a population-basedsample. In total, we tested associations between PE and 11 single nucleotidepolymorphisms in the dopamine receptor D1, D2, and D3 genes, and in the COMTgene.

Outcomes. We found no associations between dopamine receptorgene polymorphisms and PE, but two COMT-linkedloci (rs4680 and rs4818) had significant associations after correction formultiple testing.

Results. One of the COMT-gene-linkedloci that was associated with PE symptoms in the present study, rs4680, is awell-documented functional polymorphism, which causes a valine-to-methioninesubstitution. The other polymorphism, rs4818, is in high linkage disequilibriumwith the rs4680 locus, indicating that they capture the same effect.Surprisingly, the rs4680 variant that was statistically significantly moreprevalent in the PE patient group (i.e., the valine-encoding allele) haspreviously been associated with higher enzymatic activity, and therefore lowersynaptic dopamine levels.

Clinical Translation. Drugs targeting the dopaminergic system may affect PEsymptoms.

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

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.