Serotonin Transporter Gene Polymorphism Research Articles

The serotonin transporter gene polymorphism (5-HTTLPR) and irritable bowel syndrome: a meta-analysis of 25 studies

BackgroundThe results of previous studies assessing the association between the 5-HTTLPR polymorphism of serotonin transporter gene and irritable bowel syndrome (IBS) are inconsistent. The aim of this study was to clarify the association between the 5-HTTLPR mutation and the presence of IBS and its subtypes with a meta-analysis of 25 studies.MethodsA thorough search for case–control studies evaluating the association between the 5-HTTLPR polymorphism of serotonin transporter gene and the presence of IBS was carried out in four electronic databases. A meta-analysis was performed in accordance with the Cochrane Handbook for systemic reviews.ResultsA total of 25 articles with 3443 IBS cases and 3359 controls were included into our meta-analysis. No significant association was found between this polymorphism and IBS in all populations. Whereas the LL genotype was demonstrated to be a risk factor for constipation predominant IBS (IBS-C) development in the overall population (LL vs SS: OR = 1.570, 95% CI = 1.147-2.148, P = 0.005, Bon = 0.030; LL vs LS: OR = 1.658, 95% CI = 1.180-2.331, P = 0.004, Bon = 0.024; LL vs LS/SS: OR = 1.545, 95% CI = 1.187-2.012, P = 0.001, Bon = 0.006). In the analysis of different ethnicities, L allele and LL genotype were significantly associated with increased IBS-C risk in the East Asian population (L vs S: OR = 1.487, 95% CI = 1.139-1.941, P = 0.003, Bon = 0.018; LL vs SS: OR = 2.575, 95% CI = 1.741-3.808, P = 0.000, Bon = 0.000; LL vs LS: OR = 3.084, 95% CI = 2.017-4.715, P = 0.000, Bon = 0.000; LL vs LS/SS: OR = 2.759, 95% CI = 1.933-3.938, P = 0.000, Bon = 0.000), but not in the Caucasian population.ConclusionsDifferent from the conclusions of the earlier meta-analyses, the 5-HTTLPR mutation affects IBS-C but not IBS-D and IBS-M development and this effect only exists in the East Asian population but not other populations.

Does 5HTTLPR long allele prevent hospitalization? Test of Hardy–Weinberg equilibrium

Many studies suggest an association of the serotonin transporter gene polymorphism (5HTTLPR) long allele with better antidepressant treatment response than the short allele. However, there is controversy over these findings. We hypothesized that if the long allele is associated with a better outcome, we would find fewer inpatients with the long allele compared with the short allele. Chart review identified 925 depressed inpatients and 201 outpatients genotyped for 5HTTLPR. The sample was primarily White (>90%). We tested potential departures from Hardy-Weinberg equilibrium for each sample. We analyzed three independent sets of inpatient samples separately and combined, a White subgroup of 791 patients of the total 925 inpatients, and 201 outpatients. There was no departure from Hardy-Weinberg equilibrium with any of these samples. We also compared 5HTTLPR genotype prevalence between 925 inpatients and 201 outpatients, which showed no statistically significant difference.

Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder.

ObjectiveWe investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression.MethodsFinal analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed.ResultsThe 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing.ConclusionThis result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.

Lack of Association between the Serotonin Transporter (5-HTT) and Serotonin Receptor (5-HT2A) Gene Polymorphisms with Smoking Behavior among Malaysian Malays.

An insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and a polymorphism (rs6313) in the serotonin 2A receptor gene (5-HT2A) have previously been linked to smoking behavior. The objective of this study was to determine the possible association of the 5-HTTLPR and 5-HT2A gene polymorphisms with smoking behavior within a population of Malaysian male smokers (n=248) and non-smokers (n=248). The 5-HTTLPR genotypes were determined using the polymerase chain reaction (PCR) and were classified as short (S) alleles or long (L) alleles. The 5HT2A genotypes were determined using PCR-restriction fragment length polymorphisms (PCR-RFLP). No significant differences in the distribution frequencies of the alleles were found between the smokers and the non-smokers for the 5-HTTLPR polymorphism (x2 = 0.72, P>0.05) or the 5HT2A polymorphism (x2 = 0.73, P>0.05). This is the first study conducted on Malaysian Malay males regarding the association of 5-HTTLPR and 5HT2A polymorphisms and smoking behavior. However, the genes were not found to be associated with smoking behavior in our population.

Ethnicity Moderates the Association Between 5-HTTLPR and National Suicide Rates

The association between ethnicity, national suicide rates, and the functional serotonin transporter gene polymorphism (5-HTTLPR), under consideration of the role of economic indicators, national alcohol intake, and national happiness scores was analyzed with an ecologic analysis. Data on allelic frequencies of the short (s) allele from 38 countries from over 100,000 healthy screened or general population individuals were analyzed with multiple regression models. Allele frequency varied widely both within and across ethnicities and an ethnicity-based interaction between national suicide rates and 5-HTTLPR allele frequency was revealed with the s allele acting as protective factor in Caucasian and as a risk factor in non-Caucasian populations. This interaction effect underlines the importance of ethnicity as a moderating factor in the genetics of suicide.

Association between serotonin transporter gene polymorphisms and childhood asthma

Background: Asthma is a common chronic inflammatory disease of the airways in which genetic factors play a major role in its pathogenesis. High serotonin serum levels in patients with asthma suggest that serotonin is involved in the pathophysiology of the disease. Serotonin clearance is mediated by the serotonin reuptake transporter, and functional polymorphisms in this gene lead to altered serotonin reuptake efficiency. Objective: The aim of this study was to investigate the relationship between serotonin transporter gene polymorphisms and asthma. Methods: Serotonin transporter gene polymorphisms (5-HTTLPR, rs35521 and STin2.VNTR) were assessed by PCR-based methods in 100 children with mild to moderate persistent asthma and compared with 100 healthy controls. Results: There were no significant differences in allele, genotype or haplotype frequencies between patients and controls. No association was observed between SERT gene polymorphisms after stratification of patients for sex, age, spirometry indices, family history, passive smoking behavior and concomitant allergic rhinitis. Significant differences were observed in the distribution of 5-HTTLPR alleles (p = 0.025) and genotypes (p = 0.021) between patients with and without atopic dermatitis. Conclusions: Despite strong evidence suggesting the role of serotonin in the pathophysiology of asthma, we found no association between serotonin transporter gene polymorphisms and mild to moderate persistent asthma. Further serotonin transporter gene analyses in patients with severe asthma may open up new horizons in the utilization of common serotonin regulators to treat asthma, based on their pharmacogenetic effects. However, serotonin may also be indirectly influenced by emotional stress during asthma attacks.

Association between serotonin transporter (SERT) gene polymorphism and idiopathic pulmonary arterial hypertension: a meta-analysis and review of the literature

ObjectiveIdiopathic pulmonary arterial hypertension (IPAH) is a rare and often fatal disease of unknown etiology. Serotonin transporter (SERT) protein, whose genes can have two allelic forms, namely long (L) and short (S), is suspected to be related to IPAH risk. Several studies have investigated the association between SERT's different allelic forms and IPAH but showed conflicting results. A meta-analysis of published studies was performed to allow a more reliable estimate of this association. MethodsRelevant databases were searched to identify eligible studies published from 2000 to 2013. Odds ratios (OR) and 95% confidence intervals (CI) were determined for the gene–disease association using fixed or random effects models. ResultsA total of 6 studies with 451 IPAH subjects and 664 controls were included in this meta-analysis. A significant difference was found in the comparison between IPAH subjects and controls with LL vs. SS genotypes, and the pooled odds ratio (OR) with the fixed effects model was 1.446 (95% CI=1.036–2.018, p=0.030, I2=38.8%). However, no statistically significant differences were observed for LL vs. LS or LL vs. LS+SS. The pooled OR indicated no significant differences in IPAH risk between carriers of SERT L and S alleles (ORL VS. S=1.327, 95% CI=0.933–1.886, p=0.115). ConclusionThis meta-analysis provides evidence suggesting an association between the SERT L/S polymorphism and IPAH. Individuals with the LL genotype have an obviously higher risk of developing IPAH than those with the SS genotype.

Associations between endothelial nitric oxide synthase A/B, angiotensin converting enzyme I/D and serotonin transporter L/S gene polymorphisms with pulmonary hypertension in COPD patients

Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (p = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships.

A Serotonin Transporter Gene (SLC6A4) Polymorphism Is Associated with Reduced Risk of Irritable Bowel Syndrome in American and Asian Population: A Meta-Analysis

AimAssociation studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility.MethodologySystemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model.ResultsA total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population.ConclusionsThis investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.

Gene × environment interaction on intergroup bias: the role of5-HTTLPRand perceived outgroup threat

Perceived threat from outgroups is a consistent social-environmental antecedent of intergroup bias (i.e. prejudice, ingroup favoritism). The serotonin transporter gene polymorphism (5-HTTLPR) has been associated with individual variations in sensitivity to context, particularly stressful and threatening situations. Here, we examined how 5-HTTLPR and environmental factors signaling potential outgroup threat dynamically interact to shape intergroup bias. Across two studies, we provide novel evidence for a gene-environment interaction on the acquisition of intergroup bias and prejudice. Greater exposure to signals of outgroup threat, such as negative prior contact with outgroups and perceived danger from the social environment, were more predictive of intergroup bias among participants possessing at least one short allele (vs two long alleles) of 5-HTTLPR. Furthermore, this gene x environment interaction was observed for biases directed at diverse ethnic and arbitrarily-defined outgroups across measures reflecting intergroup biases in evaluation and discriminatory behavior. These findings reveal a candidate genetic mechanism for the acquisition of intergroup bias, and suggest that intergroup bias is dually inherited and transmitted through the interplay of social (i.e. contextual cues of outgroup threat) and biological mechanisms (i.e. genetic sensitivity toward threatening contexts) that regulate perceived intergroup threats.

Associations between serotonin transporter gene polymorphisms and heat pain perception in adults with chronic pain

BackgroundThe triallelic serotonin transporter gene linked polymorphic region (5-HTTLPR) has been associated with alterations in thermal pain perception. The primary aim of this study was to investigate the associations between heat pain (HP) perception and the triallelic 5-HTTLPR in a large cohort of adults with chronic pain.MethodsThe cohort included 277 adults with chronic pain who met inclusion criteria, and were consecutively admitted to an outpatient pain rehabilitation program from March 2009 through March 2010. Individuals were genotyped for the triallelic 5-HTTLPR (including rs25531) and categorized as high, intermediate, or low expressors of the serotonin transporter. Standardized measures of HP perception were obtained using a validated quantitative sensory test method of levels.ResultsThe distribution of the high, intermediate, and low expressing genotypes was 61 (22%), 149 (54%) and 67 (24%), respectively. The Hardy-Weinberg P-value was 0.204 which indicated no departure from equilibrium. A significant effect of genotype was observed for values of HP threshold (P = 0.029). Individual group comparisons showed that values of HP threshold were significantly greater in the intermediate compared to the high expressing group (P = 0.009) but not the low expressing group (P > 0.1). In a multiple variable linear regression model, the intermediate group (P = 0.034) and male sex (P = 0.021) were associated with significantly greater values of HP 0.5, but no significant genotype-by-sex interaction effect was observed.ConclusionsIn this study that involved adults with chronic pain, the intermediate triallelic 5-HTTLPR expressing group, but not the low expressing group, was associated with greater HP thresholds compared to the high expressing group.

HTR2A gene–child abuse interaction and association with a history of suicide attempt among Caucasian depressed psychiatric inpatients

BackgroundThe serotonin transporter gene polymorphism (5HTTLPR) has been associated with vulnerability for depression after exposure to stressful life event as well as with difference in treatment response to SSRI. Although the A/A genotype of the serotonin receptor SNP (rs7997012) was associated with better citalopram response than the G/G in the STAR⁎D sample, the effects of this SNP in the moderation of child abuse history on the characteristics of mental illnesses are not well understood. We examined if there are similar gene–environment interaction with the SNP. MethodsRetrospective chart review of 250 Caucasian depressed psychiatric inpatients, who had genotype for rs7997012. Subjects with each genotype were subcategorized into 2 groups with/without history of child abuse. The history of suicide attempts of each group was compared. ResultsA trend for an interaction was found between the HTR2A genotype and child abuse history influencing the prevalence of suicide attempts. Although each genotype did not show significant difference in the risk of suicide attempt when there was no abuse history, the A carriers (A/A+A/G) showed significantly higher rate of suicide attempt compared to the G/G when there is a history of child abuse (48.4% versus 22.7% respectively, p=0.0050). The likelihood ratio test from the logistic model showed a trend for an interaction between the A/A genotype and abuse history (Odds Ratio 2.10, χ2=2.49, p=0.11). LimitationsRetrospective study design and small sample size with borderline significance. ConclusionsOur findings showed a potential interaction between the HTR2A gene and stressful life events.

No interaction between serotonin transporter gene (5-HTTLPR) polymorphism and adversity on depression among Japanese children and adolescents

BackgroundIdentification of gene × environment interactions (G × E) for depression is a crucial step in ascertaining the mechanisms underpinning the disorder. Earlier studies have indicated strong genetic influences and numerous environmental risk factors. In relation to childhood and adolescent depression, evidence is accumulating that the quality of the parental environment is associated with serotonin biology in children. We hypothesized that maternal depression is a crucial environmental risk factor associated with serotonin-regulating genes.MethodsThis study was designed to ascertain the G × E interaction for diagnosis of depression in a Japanese pediatric sample. DNA samples from 55 pediatric patients with depression and 58 healthy schoolchildren were genotyped for the 5-HTT (2 short (S) alleles at the 5-HTT locus) promoter serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We examined whether an adverse parental environment, operationalized as the mother’s history of recurrent major depressive disorder, interacts with 5-HTTLPR polymorphism to predict patients’ depression symptoms.ResultsBinary logistic regression analyses revealed that maternal depression (adversity), gender, and FSIQ significantly affect the diagnosis of depression among children and adolescents. However, no main effect was found for adversity or genotype. Results of multivariable logistic regression analyses using stepwise procedure have elicited some models with a good fit index, which also suggests no interaction between 5-HTTLPR and adversity on depression.ConclusionsTo assess G × E interaction, data obtained from children and adolescents who had been carefully diagnosed categorically and data from age-matched controls were analyzed using logistic regression. Despite an equivocal interaction effect, adversity and gender showed significant main effects.

Association of serotonin transporter gene (SLC6A4) polymorphisms with schizophrenia susceptibility and symptoms in a Chinese-Han population

Schizophrenia (SZ) is a complex psychiatric disorder with a strong genetic component. The serotonin transporter (SERT), encoded by solute carrier family 6 member 4 (SLC6A4), regulates synaptic concentrations of serotonin and thereby strongly influences perception, mood, emotion, behavior, and cognition, all of which are severely disturbed in SZ. Two variable numbers of tandem repeat (VNTR) polymorphisms and several single nucleotide polymorphisms (SNPs) spread throughout SLC6A4 are involved in both neuropsychiatric diseases (including SZ) and personality traits. In this study, case-control association analysis was performed in the Chinese-Han population to identify additional allelic variants of the SLC6A4 gene that may confer susceptibility to SZ. Ten relatively common SNPs (minor allele frequency >5%) were genotyped in 528 paranoid SZ patients and 528 control subjects. Significant associations were found between SZ and the allele and genotypic frequencies of rs140700G/A (p=2.45×10(-12), 2.34×10(-11), respectively). The frequency of the A allele was lower in SZ patients (17.7%) than in controls (30.9%; OR=1.93, 95%CI=1.58-2.36). In five factor analysis of the positive and negative syndrome scale (PANSS) scores of first episode SZ patients, mean negative factor score (F2,249=3.986, p=0.02) and depression/anxiety factor score (F2, 249=8.766, p=2.11×10(-4)) were significantly different among the rs140700G/A genotypes, with both scores higher for genotype AA than AG+GG. The rs140700G/A allele of SLC6A4 is strongly associated with SZ susceptibility and symptom expression in the Chinese-Han population.

Serotonin transporter gene polymorphisms in Southwestern Iranian patients with irritable bowel syndrome

Background and study aimsIrritable bowel syndrome is a common chronic functional gastrointestinal disorder of unknown etiology. Serotonin is an important factor in sensory signaling in the brain–gut axis, which plays a key role in intestinal motility and secretion. Serotonin clearance is mediated by a specific protein called the serotonin reuptake transporter. Transcription activity of the serotonin transporter gene is affected by some polymorphisms in this gene. The aim of this study was to investigate the relationship between serotonin transporter gene polymorphisms and irritable bowel syndrome. Patients/material and methodsThe 5-HTTLPR, rs25531 and STin2VNTR polymorphisms of the serotonin transporter gene were analyzed by PCR-based methods in 50 patients with irritable bowel syndrome and 100 healthy controls. ResultsSerotonin transporter polymorphisms were similar in patients and healthy controls. There were no significant differences in allele or genotype frequencies between the two groups. ConclusionOur findings suggest that polymorphisms in the gene encoding for the serotonin transporter are not associated with irritable bowel syndrome. Interactions between environmental factors and predisposing genetic factors are important in the pathophysiology of irritable bowel syndrome, and further genetic and epigenetic research may provide novel insights into the mechanisms contributing to this disease.

The association study between the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors

Objective To explore the relevance of the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors. Methods The subjects comprised 246 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-IV) criterion for major depressive disorder(MDD). The clinical efficacy were assessed by using 17 Hamilton depression quantity (HAMD) scale after selective serotonin reuptake inhibitors(SSRIs) citalopram (20 to 60 mg/d) or paroxetine (20 to 60 mg/d) were used randomly for 1, 2, 4, 6 weeks.Polymerase chain reaction(PCR), sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE )and DNA sequencing analysis were used to detect the genotype of 5-HTT gene single nucleotide polymorphisms (SNP) of VNTR and LPR and SNPs at rs2242446 and rs5569 of NET.SPSS13.0 software were used for statistical analysis. Results (1) An association between 5-HTT LPR and the efficacy of SSRIs was found after 6 weeks in these samples (P=0.023). The clinical efficiency of LL genotype was higher than SS+ LS genotype(OR=2.225, OR95%CI=1.118, 4.427). (2) The interaction of 5-HTT LPR and NET rs5569 and the SSRIs antidepressant effects was statistical significance(P=0.01). Conclusion Preliminary study found that the interaction of 5-HTT LPR and NET rs5569 may be related to SSRIs antidepressant effects in China’s patients with MDD. Key words: Major depressive disorders; Serotonin transporter; Norepinephrine transporter; Gene polymorphisms; Interaction

Letter: serotonin transporter gene polymorphisms and the irritable bowel syndrome

Letter: serotonin transporter gene polymorphisms and the irritable bowel syndrome

Serotonin transporter gene polymorphism and its association with bipolar disorder across different ethnic groups in Malaysia

ObjectivesThe risk variants have been shown to vary substantially across populations and a genetic study in a heterogeneous population might shed a new light in the disease mechanism. This preliminary study aims to determine the frequency of the serotonin transporter gene polymorphism (5-HTTLPR) in the three main ethnic groups in Malaysia and its association with bipolar disorder. MethodsThis is a candidate gene association study of randomly selected forty five unrelated bipolar disorder probands and sixty six controls. Diagnosis was evaluated using the Mini International Neuropsychiatric Interview (M.I.N.I). The control group consisted of healthy volunteers without personal psychiatric history and family history of mood disorder. Patients' whole blood was collected for genotyping. ResultsThis study revealed that the frequency of the short variant of 5-HTTLPR in healthy control group was highest in Indians (42.9%) followed by Malays (23.5%) and was absent in Chinese. The association between the homozygous ss genotype of the 5-HTTLPR polymorphism with bipolar disorder was not found in the pooled subjects (χ2=1.52, d.f.=1, p=0.218, OR=4.67, 95% C.I.=0.69–7.58) and after stratification into Malays (p=0.315, OR=2.03, 95% CI=0.50–8.17), Indians (p=0.310; OR=0.44, 95% CI=0.21–0.92) and Chinese. ConclusionThe differences in the frequency of the short allele of 5-HTTLPR across the three main ethnic groups in Malaysia were noteworthy. The present study showed no significant association between the homozygous short variant of the 5-HTTLPR and bipolar disorder in the pooled subject and after stratification into the three main ethnic groups in Malaysia.

Association of a serotonin transporter gene polymorphism (5-HTTLPR) and stressful life events with postpartum depressive symptoms: a population-based study

We conducted a cross-sectional study nested within a cohort study with 276 postpartum women to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and the stressful life events (SLE) on the risk of postpartum depression (PPD) symptoms in a community sample. Participants were assessed between 45 and 90 days after delivery with the Edinburgh Postnatal Depression Scale (EPDS) and the Mini International Neuropsychiatric Interview (MINI). Data regarding socio-demographic variables, alcohol consumption, tobacco smoking and SLE occurring during pregnancy, were also collected. In the adjusted analysis, the women carrying the long (L) allele (LL) who experienced SLE showed higher prevalence ratios (PR) for PPD symptoms (EPDS ≥13) than those with two copies of the short (S) allele (SL) (PR = 9.91; 95% confidence interval: 1.70–57.87). In contrast, a trend of association was found between prior history of major depressive disorder (MDD) and the S allele carrier status (p = 0.07). No association was found between the formal diagnosis of current MDD and the 5-HTTLPR genotypes. In line with previous reports, we find in this sample that the L allele carrier status was associated with a heighten risk of depressive symptoms in postpartum when SLE were experienced during pregnancy.

Influence of Serotonin Transporter Gene Polymorphism (5-HTTLPR Polymorphism) on the Relation between Brain 5-HT Transporter Binding and Heart Rate Corrected Cardiac Repolarization Interval

ObjectiveSerotonin transporter gene polymorphism (5-HTTLPR polymorphism) predicts the degree of structural and functional connectivity in the brain, and less consistently the degree of vulnerability for anxiety and depressive disorders. It is less known how 5-HTTLPR polymorphism influences on the coupling between brain and neuronal cardiovascular control. The present study demonstrates the impact of 5-HTTLPR polymorphism on the relations between heart rate (HR) corrected cardiac repolarization interval (QTc interval) and the brain 5-HTT binding.Material and MethodsThirty healthy young adults (fifteen monozygotic twin pairs) (mean age 26±1.3 years, 16 females) were imagined with single-photon emission computed tomography (SPECT) using iodine-123 labeled 2β-carbomethoxy-3β-(4-iodophenyl) nortropane (nor-β-CIT). Continuous ECG recording was obtained from each participant at supine rest. Signal averaged QTc interval on continuous ECG was calculated and compared with the brain imaging results.ResultsIn the two groups [l homozygotes (n = 16, 10 females), s carriers (n = 14, 8 female)] HR and the length of QTc interval were not influenced by 5-HTTLPR polymorphism. There were no significant relations between HR and 5-HTT binding in the brain. There were significant associations between QTc interval and nor-β-CIT binding in the brain in l homozygotes, but not in s carriers (correlations for QTc interval and nor-β-CIT binding of striatum, thalamus and right temporal region were −0.8–−0.9, (p<0.0005), respectively).ConclusionThe finding of longer QTc interval with less 5-HTT binding availability in major serotonergic binding sites in l homozygotes, but not in s carriers, implicate to differentiated control of QTc interval by 5-HTTLPR polymorphism.