The Relationship Between The Polymorphisms Of 5-HT Regulatory System-related Gene And The Susceptibility Of Lifelong Premature Ejaculation

Background and Objective:Premature ejaculation（PE）is the most common male sexual dysfunction disease,which seriously affects the physical and mental health of men and women,and family harmony.5-hydroxytryptamine（5-HT）is the most important neurotransmitter that has been found to regulate ejaculation.It is widely distributed in the ejaculation nerve center and peripheral ejaculation related organs to regulate ejaculation activity.The speed limit and the regulation of 5-HT by the synthetic enzyme（Tryptophanhydroxylase,TPH）,receptor（5-HT1A and 5-HT2C）and transporter（serotonin transporter,5-HTT）gene,affects 5-HT concen-trations in the blood.Recently,the exploration of PE related 5-HT has been a hot topic.It is found that the PE is influenced by genetic factors.Among the four types of PE,lifelong PE（LPE）is the most associated with genetics.Therefore,the multiple single nucleotide sites of 5-HT synthesis rate-limiting enzyme2（TPH2）,receptor（HTR1A and HTR2C）and 5-HTT were analyzed and evaluated to investigate the association between the polymorphisms of5-HT regulatory system genes and the susceptibility of LPE using a case-control study,and hence to provide new genetic and genetic polymorphism evidence for the pathogenesis of LPE,as well as scientific basis and clues for finding new therapeutic LPE targets,and further to enrich the gene pool of biological resources in ChinaMethods:1.The single nucleotide polymorphisms（SNPs）genotypes of5-HTT coded by SLC6A4 in 91 LPE patients（case group）and 362healthy persons without PE（control group）were analyzed by Agena MassARRAY.Then genetic model and haplotype analysis were used to investigate the association between polymorphism and LPE risk.2.The10 SNPs genotypes of TPH2 in 189 LPE（case group）and 362 healthy persons without PE（control group）were analyzed by Agena MassARRAY,and the ratio（ORs）and 95%confidence interval（CIs）were calculated by logistic regression analysis to evaluate the relationship between the TPH2 polymorphism and the LPE risk.3.The 15 SNPs genotypes of HTR1A and HTR2C in 189 LPE（case group）and 362healthy persons without PE（control group）were analyzed by Agena MassARRAY,and the ratio（ORs）and 95%confidence interval（CIs）were calculated by logistic regression analysis to evaluate the relationship between the 5-HTR polymorphism and the LPE risk.4.The plasma concentrations of 5-HT,leptin and folic acid were determined by enzyme-linked immunoassay,and the relationship between their concentrations and three related genes of 5-HT regulatory system was evaluated in LPE patients.Results:1.Allele T of 5-HTT-rs9303628 on SLC6A4 gene,genotype T/T and C/T-T/T in allele model were significantly associated with reduced risk of LPE.The allele T and genotype C/T-T/T of5-HTT-rs2054847 reduced the risk of LPE in co-dominant and dominant models,respectively.In addition,haplotype A_rs9303628C_rs2054847 was significantly associated with a reduced risk of LPE.2.The G allelic basis of TPH2-rs11178996 reduces the risk of LPE in co-dominant,dominant and additive models.Haplotype analysis showed that G_rs11179041T_rs10879352 reduced the risk of LPE.Moreover,TPH2 gene polymorphisms were significantly associated with leptin,5-HT and folic acid levels.3.HTR1A-rs6295 increased the risk of LPE in recessive models（G/G genotype）,while no association was found between HTR2C gene polymorphism and the risk of LPE.Conclusion:1.The 5-HTT-rs9303628 and 5-HTTrs2054847 in the SLC6A4 encoded 5-HTT genes is found to be associated with the reduced risk of LPE onset.2.Just like 5-HTT,the TPH2-rs11178996 is confirmed to be associated with the decreasing of LPE risk,and the haplotype G_rs11179041T_rs10879352 is related to the reduced risk of LPE onset.Additionally,TPH2 gene polymorphisms are significantly associated with leptin,5-HT,and folic acid levels.It is the first time to find that the HTR1A-rs6295 maybe incresae the susceptibility of LPE,however,the SNPs in HTR2C have nothing with the onset of LPE.To sum up,this study first testify the distribution and difference of 5-HT regulation system related gene polymorphisms of LPE in Chinese Han nationality population,and comprehensively and systematically clarified the correlation between 5-HT regulation system related gene polymorphisms and the LPE pathogenesis.It reveals the types of genetic polymorphisms in Chinese nationality for the first time,which is of great scientific significance to enrich the connotation of biological resource gene pool in China.