Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
Department of Psychology, University of Turku, Turku, Finland; QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
J Sex Med. 2017 Dec;14(12):1558-1565. doi: 10.1016/j.jsxm.2017.11.002.
Studies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE).
To investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE.
PE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 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 gene.
We found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMT-linked loci (rs4680 and rs4818) had significant associations after correction for multiple testing.
1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that 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 group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels.
Drugs targeting the dopaminergic system could affect PE symptoms.
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 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 used samples of 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 function.
We report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated. Jern P, Johansson A, Strohmaier J, et al. Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation. J Sex Med 2017;14:1558-1565.
研究表明，多巴胺在引发射精的神经生物学机制中起作用，这导致科学家假设多巴胺相关的遗传多态性可能导致早泄（PE）的症状。
研究多巴胺受体和儿茶酚-O-甲基转移酶（COMT；一种参与多巴胺代谢的酶）基因相关多态性与 PE 之间的关联。
通过专门从事性医学的医生进行临床诊断来确定患者组的 PE 状态。还报告了来自经过验证的问卷的自我报告的 PE 症状。从基于人群的样本中收集了 149 名 PE 患者和 1022 名对照者的唾液样本。我们总共测试了多巴胺受体 D1、D2 和 D3 基因和 COMT 基因中的 11 个单核苷酸多态性与 PE 之间的关联。
我们没有发现多巴胺受体基因多态性与 PE 之间的关联，但在进行多次测试校正后，有 2 个 COMT 相关基因座（rs4680 和 rs4818）存在显著关联。在本研究中与 PE 症状相关的 1 个 COMT 基因座，rs4680 是一个已被充分记录的功能多态性，可导致缬氨酸到蛋氨酸取代。另一个多态性 rs4818 与 rs4680 基因座高度连锁不平衡，表明它们捕获了相同的效果。令人惊讶的是，在 PE 组中统计学上更常见的 rs4680 变体（即编码缬氨酸的等位基因）与更高的酶活性相关，因此突触多巴胺水平更低。
针对多巴胺能系统的药物可能会影响 PE 症状。
本研究没有可供复制的样本；因此，我们的研究结果应谨慎解释。此外，我们研究的一个局限性是遗传关联研究中遗传关联研究的样本较小（尽管应该指出的是，具有 PE 症状表型信息的遗传上信息丰富的样本很少，并且大多数以前的 PE 遗传关联研究都使用了相似或更小的样本）。然而，我们的结果是合理的：我们报告了精神科研究中最广泛研究和理解的遗传多态性之一与 PE 之间的关联，我们的结果与多巴胺影响人类射精功能的长期假设一致。
我们报告了 2 个 COMT 基因座与 PE 症状之间的关联，但我们的结果应在独立复制之前谨慎对待。Jern P，Johansson A，Strohmaier J，等。初步证据表明儿茶酚-O-甲基转移酶（COMT）基因变异与早泄有关。J 性别医学 2017;14:1558-1565。
