A Meta-Analysis of the Effects of the 5-Hydroxytryptamine Transporter Gene-Linked Promoter Region Polymorphism on Susceptibility to Lifelong Premature Ejaculation

Zhu, Ling; Mi, Yuanyuan; You, Xiaoming; Wu, Sheng; Shao, Hongbao; Dai, Feng; Peng, Tao; Feng, Qin; Feng, Na

doi:10.1371/journal.pone.0054994

Cited by 24 publications

(35 citation statements)

References 39 publications

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“…In accordance with this prediction, one study found that polymorphism in the serotonin transporter promoter region (5-HTTLPR) is associated with ejaculation latency time (Janssen et al 2009). A meta-analysis found significant associations between the risk of premature ejaculation and 5-HTTLPR polymorphism (Zhu et al 2013). Furthermore, another study found that polymorphism in the dopamine transporter gene (DAT1) is associated with premature ejaculation (Santilla et al 2010see also Safarinejad 2011.…”

Section: Predictions and Evidencementioning

confidence: 87%

Sexual Dysfunctions in Men: An Evolutionary Perspective

Apostolou

2015

Evolutionary Psychological Science

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Successful sexual intercourse is a prerequisite for successful reproduction, a fact that translates into strong evolutionary pressures being exercised on mechanisms that regulate sexual functioning to work optimally. In effect, selection forces would remove from the gene pool any alleles that predispose for sexual dysfunctions, limiting their prevalence to very low levels. But this did not happen with epidemiological studies indicating that sexual dysfunctions are common, with approximately one in three men facing such a difficulty. This raises the question why evolutionary forces have allowed such variation in sexual functioning given its importance in reproduction. The present paper attempts to address this question by applying three evolutionary models on anthropological and historical evidence that depicts the ancestral human condition. It is argued that the high prevalence of sexual dysfunctions in men is predominantly explained by the mismatch between ancestral and modern environments, with selection forces not having sufficient time to optimize sexual functioning mechanisms to the demands of modern conditions. The proposed evolutionary framework is employed to derive predictions which are examined against the available evidence on sexual dysfunctions.

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Section: Predictions and Evidencementioning

confidence: 87%

Sexual Dysfunctions in Men: An Evolutionary Perspective

Apostolou

2015

Evolutionary Psychological Science

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“…With the also lower OR found in LL versus SS genotype frequencies in all Caucasian patients versus controls (OR = 0.88; CI 0.80–0.98), and lower OR also found in LL+LS versus SS genotype frequencies in Caucasian patients versus controls (OR = 0.83; CI 0.70–1.00), Zhu et al [13] interpreted these results as that SS genotype and/or S-allele are risk factors of lifelong PE. And therefore they concluded that LL genotype and/or L-allele might be protecting factors for lifelong PE.…”

Section: Discussionmentioning

confidence: 97%

“…Instead, as Zhu et al [13] have pooled the ORs of 5 (Caucasian) studies, including the two studies not-in-HWE (Safarinejad and Ozbek), they erroneously calculated a low OR for all five of these studies.…”

Section: Discussionmentioning

confidence: 99%

Measurement Errors in Polymerase Chain Reaction Are a Confounding Factor for a Correct Interpretation of 5-HTTLPR Polymorphism Effects on Lifelong Premature Ejaculation: A Critical Analysis of a Previously Published Meta-Analysis of Six Studies

et al. 2014

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ObjectiveTo analyze a recently published meta-analysis of six studies on 5-HTTLPR polymorphism and lifelong premature ejaculation (PE).MethodsCalculation of fraction observed and expected genotype frequencies and Hardy Weinberg equilibrium (HWE) of cases and controls. LL,SL and SS genotype frequencies of patients were subtracted from genotype frequencies of an ideal population (LL25%, SL50%, SS25%, p = 1 for HWE). Analysis of PCRs of six studies and re-analysis of the analysis and Odds ratios (ORs) reported in the recently published meta-analysis.ResultsThree studies deviated from HWE in patients and one study deviated from HWE in controls. In three studies in-HWE the mean deviation of genotype frequencies from a theoretical population not-deviating from HWE was small: LL(1.7%), SL(−2.3%), SS(0.6%). In three studies not-in-HWE the mean deviation of genotype frequencies was high: LL(−3.3%), SL(−18.5%) and SS(21.8%) with very low percentage SL genotype concurrent with very high percentage SS genotype. The most serious PCR deviations were reported in the three not-in-HWE studies. The three in-HWE studies had normal OR. In contrast, the three not-in-HWE studies had a low OR.ConclusionsIn three studies not-in-HWE and with very low OR, inadequate PCR analysis and/or inadequate interpretation of its gel electrophoresis resulted in very low SL and a resulting shift to very high SS genotype frequency outcome. Consequently, PCRs of these three studies are not reliable. Failure to note the inadequacy of PCR tests makes such PCRs a confounding factor in clinical interpretation of genetic studies. Currently, a meta-analysis can only be performed on three studies-in-HWE. However, based on the three studies-in-HWE with OR of about 1 there is not any indication that in men with lifelong PE the frequency of LL,SL and SS genotype deviates from the general male population and/or that the SL or SS genotype is in any way associated with lifelong PE.

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“…Because of the effectiveness of the serotoninergic drugs in PE, researchers focused on the serotoninergic genes as the promoter region of the 5-HT transporter gene, which has been the most extensively studied (91)(92)(93)(94). Positive associations equal negative associations, and the issue should be considered at least controversial.…”

Section: Risk Factors the Role Of The Geneticsmentioning

confidence: 99%

“…However, the same association was reported by others but in the opposite direction (92,95). Even a metaanalysis on these data (93) has been criticized (96).…”

Section: Risk Factors the Role Of The Geneticsmentioning

confidence: 99%