Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Effect of Bacillus subtilis,Enterococcus faecium,and Enterococcus faecalis supernatants on serotonin transporter expression in cells and tissues

BACKGROUND Bacillus subtilis(B.subtilis),Enterococcus faecium(E.faecium),and Enterococcus faecalis(E.faecalis)are probiotics that are widely used in the clinical treatment of irritable bowel syndrome(IBS).Whether the supernatants of these three probiotics can improve gastrointestinal sensation and movement by regulating the serotonin transporter(SERT)expression needs to be clarified.AIM To investigate whether B.subtilis,E.faecium,and E.faecalis supernatants can upregulate SERT expression in vitro and in vivo.METHODS Caco-2 and HT-29 cells were stimulated with probiotic culture supernatants for 12 and 24 h,respectively.A male Sprague-Dawley rat model of post-infectious irritable bowel syndrome(PI-IBS)was established and the rats were treated with phosphate-buffered saline(group A)and three probiotics culture supernatants(groups B,C,and D)for 4 wk.The levels of SERT were detected by quantitative PCR and western blotting.RESULTS The levels of SERT at post-treatment 12 and 24 h were significantly elevated in Caco-2 cells treated with B.subtilis supernatant compared with those in the control group(aP<0.05).Those levels were markedly upregulated in Caco-2 cells stimulated with E.faecium and E.faecalis supernatants at 24 h(aP<0.05).In addition,SERT expression in groups B,C,and D was significantly higher than that in group A in the 2nd wk(aP<0.05).Increased SERT expression was only found in group D in the 3rd wk(aP<0.05).However,there was no significant difference in SERT expression between the groups in the last week(P>0.05).CONCLUSION The supernatants of B.subtilis,E.faecium,and E.faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS.

Association between serotonin transporter gene polymorphisms and non-lesional temporal lobe epilepsy in a Chinese Han population

Serotonin （5-hydroxytryptamine, 5-HT） influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter （5-HTT） is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region （5-H-I-FLPR） in patients with non-lesional temporal lobe epilepsy and normal controls （P〉 0.05）. Frequencies of the 5-H1-1- intron 2 variable number tandem repeat （5-HTTVNTR） 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls （P 〈 0.01）. The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 （95% Cl, 1.096 1.880） in patients carrying allele 12 （P 〈 0.05）. Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.

Association of serotonin transporter gene polymorphisms and major depressive disorder in Chinese Han population

BACKGROUND： Serotonin transporter （5-HTT） polymorphisms comprise 5-HTT gene-linked polymorphism region （5-HTTLPR） and variable number of tandem repeats （VNTR）. Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the ＂S＂ allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE： To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING： Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS： A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale （24 items） ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS： Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES： 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS： No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls （P 〉 0.05）. However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected （P 〈 0.01 ）. The Stin2.10 allele and 10/10 genotype associated with major depressive disorder （OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01）. CONCLUSION： Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.

Determination of Synthetic Impurities and Metabolic Products of F-ADAM, a Positron Emission Tomography Imaging Agent for Serotonin Transporter (SERT) Using HPLC-Tandem Mass Spectrometry

A high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analytical method was developed to determine the identity of impurities resulting from the synthesis of N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzyl-amine (F-ADAM), as well as its metabolic products by rat liver microsomes. 18F-ADAM is an important positive electron emission ligand commonly employed as a radio-imaging agent for serotonin transporter (SERT) in the brain. F-ADAM and its derivatives were separated using HPLC on a C4-phenyl column with an ammonium formate aqueous buffer/acetonitrile programmed mobile phase. Synthetic contaminants and metabolic products were identified using fragmentation spectra obtained by tandem mass spectrometry. We show that F-ADAM is unstable in methanol, and propose the use of acetonitrile to generate optimal chromatogram. A Cl-substituted species was found to be the major impurity resulting from the F-ADAM synthetic process. The metabolic products of F-ADAM by rat liver microsomes were characterized by oxidization of the sulfur moiety to sulfoxide, demethylation of the dimethylamine moiety, and oxidative defluorination/deamination. These results elucidate the by-products of F-ADAM synthetic and metabolic processes, and provide direction for the application of this imaging agent to biosystems properly.

Evaluation of the 5-HTTLPR and 5-HTTVNTR Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Objective: The purpose of the present study was to evaluate the association between the 5-HTTLPR and 5-HTTVNTR polymorphisms in the serotonin transporter gene (SLC6A4) in Brazilian women with diagnosed postpartum depression (PPD) and the presence of depressive symptoms. Method: The cohort consisted of 128 white women who were charac-terized based on skin color and morphological characteristics. The Beck Depression Inventory was used to diagnose PPD and to score the depressive symptoms. The 5-HTTLPR and 5-HTTVNTR polymorphisms were analyzed by PCR-based methods. Results: No association was observed between the PPD diagnosis and either the 5-HTTLPR (p = 0.48) or the 5-HTTVNTR (p = 0.77) polymorphism. When the polymorphisms were analyzed together with haplotype data, the analyses demonstrated that women carriers of the L-12/L-12 diplotype have lower Beck Depression Inventory scores than women carrying other diplotypes (p = 0.04). Discussion: Few studies have investigated the association of SLC6A4 polymorphisms with PPD, and the role of 5-HTTLPR and 5-HTTVNTR polymorphisms in PPD susceptibility has not been established to date. Therefore, our findings link the haplotypes of these two variants with depression symptoms, thereby contributing to our understanding of PPD susceptibility.

Exploring unbinding mechanism of drugs from SERT via molecular dynamics simulation and its implication in antidepressants

The human serotonin transporter(SERT)terminates neurotransmission by removing serotonin from the synaptic cleft,which is an essential process that plays an important role in depression.In addition to natural substrate serotonin,SERT is also the target of the abused drug cocaine and,clinically used antidepressants,escitalopram,and paroxetine.To date,few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT.In this article,the conserved property of the orthosteric and allosteric sites(S1 and S2)of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics(MD)simulations.The residues Tyr95 and Ser438 located within the S1 site,and Arg104 located within the S2 site in SERT illustrate conserved interactions(hydrogen bonds and hydrophobic interactions),as responses to selective serotonin reuptake inhibitors.Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further,electrostatic interactions highlighted escitalopram as a potent antidepressant.We found that cocaine,escitalopram,and paroxetine,whether the S1 site or the S2 site,were more competitive.According to this potential of mean force(PMF)simulations,the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were~18A for serotonin and~22 A for the above-mentioned three drugs.Furthermore,the distance between the natural substrate serotonin and cocaine(or escitalopram)at the allosteric site was~3A.Thus,it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or the S2 site of SERT in comparison to the substrate.Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT,this study observed a broad pathway in which serotonin,cocaine,escitalopram(at the S1 site),and paroxetine all were pulled out to an opening between MT1b and MT6a,which may be helpful to understand the dissociation mechanism of antidepressants.

1-[2-(2-Methoxyphenylthio) benzyl]-4-arylpiperazines derivatives:Synthesis and evaluation for dual 5-HT_(1A)/SSRI activities

A series of 1-[2-（2-methoxyphenylthio） benzyl]-4-arylpiperazines derivatives was designed and synthesized based on 5-HT1A/ SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

1-(N-(2-(2-Methoxyphenylthio)benzyl)-N-methylamino-3-aryloxypropan-2-ols:Synthesis and evaluation for dual 5-HT_(1A)/SSRI activities

A series of 1-（N-（2-（2-methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/ 5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Abuse-related effects of synthetic cathinones：importance of DAT/SERT relationships

OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally.Chemists skirt these laws by altering the chemical structures of first-generation cathinones(ie,MDPV,methylone,and mephedrone),resulting in second-generation cathinones(eg,α-PVP,α-PPP,MDPPP,and MDPBP).Although MDPV is a more effective reinforcer than cocaine,little is known about the reinforcing effectiveness of secondgeneration cathinones.To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers.METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains.The relative reinforcing effectiveness of intravenously self-administered MDPV,MDPBP,MDPPP,α-PVP,α-PPP,and cocaine were directly compared through evaluations of (1)dose-response curves under a progressive ratio(PR)schedule of reinforcement and (2)demand curves obtained for each drug in male Sprague-Dawley rats.RESULTS Rank order selectivity for DAT/SERT wasα-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine.Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement(α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine)and the essential value obtained for each drug in demand analyses(α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine)suggest relative reinforcing effectiveness is related to DAT/SERT selectivity.CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.

PROPOFOL DECREASES ^(125)I-β-CIT BINDING TO THE DOPAMINE TRANSPORTER

Objective To determine the changes of brain dopamine transporter in mice receiving propofol anesthesia, 125I-β-CIT binding sites were observed at different time course. Methods 1. Twenty-seven normal Kunming mice were randomizedly divided into 3 groups (n = 9 ) and received intraperitoneal injection of propofol 100, 200 mg/kg and 10% intralipid (as control ) respetively. The time of losing righting reflex and displaying excitatory symptoms were recorded within 10min after administration. 2. Sixty Kunming mice were randomizedly assigned into 2 groups (n = 30 ). The mice were given 125I-β-CIT intravenously and propofol 200mg/kg or 10% intralipid (as control ) intraperitoneally. Five mice in every group were killed at different time course and their brain removed to isolate cerebellar, hypothalamus, striatum and cerebral cones. After weighting brain tissues, the radioactivity of 125I-β-CIT in different brain tissue was measured. Results 1. The time of losing righting reflex wes reduced from 319. 167 ± 88. 228s in proud 100mg/kg group to 231. 667 ± 46. 233s in propofol 200mg/kg group, and it fell from 193. 75 ± 27. 233s to 145. 556 ± 27. 437s for presenting excitatory activity. 2. Propofol intraperitoneal groups significantly decreed the combination of 125I-β-CIT and dopamine transporter in the striatum (P< 0. 01 ) and cerebral cortex (P < 0. 05) 120min after injection of propofol compared with the control group. But propofol increased the binding (P< 0. 05 ) in the striatum 30min after injection. theclusion The inhibitive effect of propofol on dopamine transporter to uptake dopamine in mice brain may contribute to some anesthetic mechanisms.

Changes of Serotonin （5-HT）, 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression, Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Background： To evaluate whether serotonin （5-HT）, 5-HT2A receptor （5-HT2AR）, and 5-HT transporter （serotonin transporter [SERT]） are associated with different disease states of depression, myocardial infarction （MI） and MI co-exist with depression in Sprague-Dawley rats. Methods： After established the animal model of four groups include control, depression, MI and MI with depression, we measured 5-HT, 5-HT2AR and SERT from serum and platelet lysate.Results： The serum concentration of 5-HT in depression rats decreased significantly compared with the control group （303.25 ± 9.99 vs. 352.98 ±13.73; P =0.000）, while that in MI group increased （381.78 ±14.17 vs. 352.98 ±13.73; P = 0.000）. However, the depression ＋ MI group had no change compared with control group （360.62 ±11.40 vs. 352.98 ±13.73; P = 0.036）. The changes of the platelet concentration of 5-HT in the depression, MI, and depression ＋ MI group were different from that of serum. The levels of 5-HT in above three groups were lower than that in the control group （380.40 ± 17.90, 387.75 ±22.28,246.40 ±18.99 vs. 500.29 ±20.91 ; P = 0.000）. The platelet lysate concentration of 5-HT2AR increased in depression group, MI group, and depression ＋ MI group compared with the control group （370.75 ±14.75,393.47 ±15.73,446.66 ±18.86 vs. 273.66 ±16.90; P= 0.000）. The serum and platelet concentration of SERT in the depression group, MI group and depression ＋ MI group were all increased compared with the control group （527.51 ±28.32, 602.02 ±23.32, 734.76 ±29.59 vs. 490.56 ±16.90; P 0,047, P = 0.000, P = 0.000 in each and 906.38 ±51.84, 897.33 ±60.34, 1030.17 ±58.73 vs. 708.62 ±51.15; P = 0.000 in each）. Conclusions： The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression. Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

Effects of Ginseng Fruit Saponins on Serotonin System in Sprague-Dawley Rats with Myocardial Infarction, Depression, and Myocardial Infarction Complicated with Depression

Background： Our previous studies have demonstrated that the levels of 5-hydroxytryptamine （5-HT） and 5-HT 2A receptor （5-HT2AR） in serum and platelet were associated with depression and myocardial infarction （MI）, and pretreatment with ginseng fruit saponins （GFS） before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley （SD） rats with MI, depression, and MI ＋ depression were evaluated. Methods： A total of eighty SD rats were allocated to four groups： MI, depression, MI ＋ depression, and control groups （n = 20 in each group）. Each group included two subgroups （n = 10 in each subgroup）： Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT2AR, and serotonin transporter （SERT） were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively. Results： Compared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI ＋ depression groups （serum： all P = 0.000; platelet lysate： P = 0.002, 0.000, 0.000, respectively）. However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups （P = 0.025 and 0.044 respectively）, and no significant difference was observed between saline and GFS treatment subgroups in MI ＋ depression group （P = 0.663）. Compared with that in GFS treatment subgroup of control group, the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI ＋ depression groups （all P = 0.000）. Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI ＋ depression groups （P = 0.009, 0.038, and P = 0.001, respectively）, while the SERT levels of platelet lysate significantly decreased in GFS treatment subgroup of MI group （P = 0.000）, significantly increased in GFS treatment subgroup of depression group （P = 0.019）, and slightly changed in GFS treatment subgroup of MI ＋ depression group （P = 0.219）. No significant changes for SERT levels in brain homogenate could be found between the saline and GFS treatment subgroups in MI, depression, and MI ＋ depression groups （P = 0.421, 0.076 and P = 0.642）. Conclusions： This study indicated that GFS might inhibit the reuptake of 5-HT from serum to platelet according to decreased 5-HT2AR in platelet and SERT in serum and platelet. The change of 5-HT in serum after GFS treatment was inconsistent with that in the brain. It seemed that GFS could not pass through the blood-brain barrier to affect the central serotonergic system.

Authors' response to “Maternal age as a potential explanation of the role of the L allele of the serotonin transporter gene in anxiety and depression in Asians”

In the letter to the editor, Dr. Comings et al. proposed a potential explanation of our findings that the L allele rather than S allele of 5-HTTLPR was associated with higher anxiety levels and reduced amygdala-prefrontal cortex （PFC） connectivity in Han Chinese[1], which demonstrated an ＇allele reversal＇ in the genetics of the 5-HTTLPR gene in Asians versus Caucasians. The authors alleged that this ＇allele reversal＇ might simply result from maternal age and suggested that we test this on our datasets. Unfortunately,

Epigenetic Regulation of Serotonin Transporter in Psychiatric Disorders

SLC6A4 （solute carrier family 6, member 4） gene encodes a serotonin transporter （5-hydroxytryptamine transporter, HTT）, which transports synaptic serotonin into presynaptic terminal. SLC6A4 is known to be the target of antidepressants such as selective serotonin reuptake inhibitors （SSRIs）. Inhibition of HTT increases synaptic serotonin concentration and thereby exerts antidepressant efficacy. A large number of genetic studies suggest the contribution of genetic variations of SLC6A4 to various psychiatric disorders. The most studied genetic variation, HTT-linked polymorphic region （HTTLPR）,

Meta‑analysis of the Association between Serotonin Transporter Polymorphisms and Sudden Infant Death Syndrome

The serotonin transporter(5‑HTT)gene has been considered one of the risk factors for sudden infant death syndrome(SIDS),but the association remains unconfirmed.This meta‑analysis was performed to quantitatively summarize the evidence for such a relationship.PubMed,EMBASE,and China National Knowledge Infrastructure databases were searched for eligible studies within a range of published years from 1990 to December 2015.The odds ratios(ORs)with 95%confidence intervals(CIs)were used to assess the different associations.A total of 8 studies with 624 cases and 796 controls were included for 5‑HTT promoter polymorphism,5 studies with 418 cases and 542 controls for intron 2,and 3 studies with 253 cases and 334 controls for haplotype.The pooled examinations showed an overall increased SIDS risk for the 5‑HTT promoter polymorphism(OR=1.65,95%CI=1.03–2.63,P=0.035 for LL vs.LS and SS;OR=1.46,95%CI=1.04–2.04,P=0.028 for L vs.S),but no association(OR=1.00,95%CI=0.75–1.33,P=0.994 for 10+9 carriers vs.12/12;OR=0.97,95%CI=0.79–1.19,P=0.753 for 10+9 vs.12)for intron 2 polymorphism,and an unreliable association(OR=0.52,95%CI=0.31–0.87,P=0.013)for S‑9 and S‑10 haplotypes.This meta‑analysis suggests that the L allele or LL homozygote of 5‑HTT promoter polymorphism has an increased risk for SIDS,while intron 2 polymorphism has no association with SIDS.

Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males

Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter （5-HTT） is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-linked polymorphic region （5-HTTLPR）. Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males. Methods Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects. Results The proportion of L/L （15.3% vs 5.2%） and S/L （50.0% vs 33.3%） genotypes was significantly higher in the smokers than that in the non-smokers （X^2=21.9; P 〈0.01）. The odds ratio （OR） adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 （95%CI 1.78-4.80）. In smokers, the number of cigarettes/day （L/L vs S/L vs S/S： 28±12 vs 20±8 vs 16±6, X^2=18.5, P 〈0.01）, smoking index （L/L vs S/L vs S/S： 561±446 vs 393±341 vs 237±201, X^2=12.5, P 〈0.01） and score on the Fagerstrom test for nicotine dependence （FTND） （L/L vs S/L vs S/S： 7.8±1.6 vs 6.2±2.5 vs 3.5±2.1, X2=48.3, P 〈0.01） were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype. There were no significant differences in the proportion of starting smoking before 20 years old （P=0.219） and those who succeeded in quitting smoking for more than 1 month （P=-0.456） between individuals with different 5-HTTLPR genotypes in smokers. Conclusions 5-HTTLPR polymorphism may be associated with susceptibility to cigarette smoking in Chinese males. The proportion of the L/L and S/L genotype in smokers was higher than that in non-smokers. In smokers, the level of nicotine dependence and resultant cigarettes consumption may be much higher in individuals with an L/L or S/L genotype than those with the S/S genotype.