Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

Özbek, Emin; Ötünçtemur, Alper; Şimşek, Abdülmuttalip; Polat, Emre Can; Özcan, Levent; Köse, Osman; Çekmen, Mustafa

doi:10.6061/clinics/2014(11)01

Cited by 10 publications

(8 citation statements)

References 24 publications

(21 reference statements)

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“…Therefore, 5-HT was considered an anorexigenic neurotransmitter and has become a target for anti-obesity treatment. 73…”

Section: Dovepressmentioning

confidence: 99%

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature

Maierean¹,

Bordea²,

Sălăgean³

et al. 2021

NSS

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Background: Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA. Objective: To examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity. Data Sources: A systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case-control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep. Study Eligibility Criteria: The inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added-English articles published in the last 15 years. Studies that were not included were reviews and case reports. Study Appraisal and Synthesis Methods: In order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list. Results: The search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT)-variable number of tandem repeats (VNTR) and linked polymorphic region (LPR)-are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long

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“…Therefore, 5-HT was considered an anorexigenic neurotransmitter and has become a target for anti-obesity treatment. 73…”

Section: Dovepressmentioning

confidence: 99%

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature

Maierean¹,

Bordea²,

Sălăgean³

et al. 2021

NSS

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“…Pharmacogenetic studies of SSRI efficacy for this indication may provide insight into SSRI tolerability in patients treated for more traditional indications. In 69 patients with premature ejaculation treated with paroxetine, the 5‐HTTLPR S allele was more common in responders (i.e., more frequent delayed ejaculation, p<0.05) . To the contrary, in a study of 54 Dutch men with premature ejaculation treated with paroxetine, 5‐HTTLPR genotype was not associated with fold change in intravaginal ejaculator latency time (p=0.83) …”

Section: Resultsmentioning

confidence: 98%

“…In 69 patients with premature ejaculation treated with paroxetine, the 5-HTTLPR S allele was more common in responders (i.e., more frequent delayed ejaculation, p<0.05). 46 To the contrary, in a study of 54 Dutch men with premature ejaculation treated with paroxetine, 5-HTTLPR genotype was not associated with fold change in intravaginal ejaculator latency time (p=0.83). 47 It is not surprising that results for this phenotype are conflicting, as sexual functioning is a complex phenotype, with potential for dysfunction in desire, arousal, orgasm, or satisfaction.…”

Section: Sexual Dysfunction Adverse Eventsmentioning

confidence: 94%

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

2017

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Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes. Four online databases (PubMed, Cochrane CENTRAL, PsycINFO, and PharmGKB) were searched for articles on polymorphisms of SLC6A4 including 5-HTTLPR and STin2 by using a systematic approach. Specific and general psychopharmacology terms, along with adverse effect and tolerability concepts, added to the search strategy. The Human Gene Mutation Database was checked for additional references. Forty studies met the inclusion criteria. While null and occasionally opposite associations are reported, the low expression 5-HTTLPR S allele is generally associated with greater adverse drug reaction burden during SSRI therapy. The most convincing evidence is in studies of antidepressant-induced mania and gastrointestinal adverse events. Studies of STin2 are sparse and have conflicting findings. In conclusion, the S allele of 5-HTTLPR may be predictive of increased adverse event burden, and this effect appears specific to certain classes of adverse events. Limitations and challenges in interpreting this body of evidence include assay errors, dissimilar grouping of genotypes, the role of ethnicity in associations, and study methodological differences. The clinical utility of serotonin transporter genotypes is not yet delineated but will ultimately depend on genotypic effects on both tolerability and efficacy of SSRIs.

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“…Regarding the treatment of SSRIs in LPE, Janssen et al [ 25 ] investigated the association between the 5-HTTLPR polymorphism and the response to paroxetine in men with LPE, reporting no difference in 5-HTTLPR allelic and genotypic variations. Ozbek et al [ 26 ] evaluated the association between the 5-HTTLPR polymorphism and 20-mg paroxetine-induced ejaculation delay in LPE patients. The study showed the S allele was significantly more frequent in responders.…”

Section: Discussionmentioning

confidence: 99%

Biallelic and Triallelic 5-Hydroxytyramine Transporter Gene-Linked Polymorphic Region (5- HTTLPR) Polymorphisms and Their Relationship with Lifelong Premature Ejaculation: A Case-Control Study in a Chinese Population

et al. 2016

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BackgroundThis study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications.Material/MethodsA total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients.ResultsThe patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L’L’ genotype (OR=0.37; 95%CI=0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes.ConclusionsContrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies.

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Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

Cited by 10 publications

References 24 publications

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

Biallelic and Triallelic 5-Hydroxytyramine Transporter Gene-Linked Polymorphic Region (5- HTTLPR) Polymorphisms and Their Relationship with Lifelong Premature Ejaculation: A Case-Control Study in a Chinese Population

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