Transporter Gene Promoter Region Polymorphism Research Articles

Meta-analysis of 5-hydroxytryptamine transporter gene promoter region polymorphism and post-stroke depression.

ObjectiveTo investigate the relationship between 5-hydroxytryptamine transporter gene promoter region (5-HTTLPR) gene polymorphism and post-stroke depression (PSD).MethodsWe searched the CNKI, China Science and Technology Journal, China WanFang, PubMed, Embase, and Web of Science databases for studies of the relationship between 5-HTTLPR polymorphism and PSD. Data were evaluated using Stata software.ResultsThe L allele was significantly related to the S allele (OR = 0.57, 95% confidence interval (CI) 0.49–0.65). The dominant genotype LL + LS was related to SS (OR = 0.48, 95%CI 0.39–0.59), the recessive genotype LL was related to LS + SS (OR = 0.39, 95%CI: 0.30–0.51), the homozygous genotype LL was related to SS (OR = 0.24, 95%CI 0.18–0.33), and the heterozygous genotype LS was related to SS (OR = 0.55, 95 CI 0.44–0.68). All the differences were significant. Ethnicity subgroup analysis showed significant differences among the five genotypes in both Asians and Caucasians. Hardy–Weinberg equilibrium (HWE) subgroup analysis showed that, after removal of a non-HWE-conforming control group, all five genotypes were significant and genotypes LL, LS + LL, and LS and L allele had beneficial effects on recovery from PSD.Conclusion5-HTTLPR gene polymorphism is strongly associated with PSD, and the LL, LS + LL, and LS genotypes and L allele may protect against this condition.

Interaction between a serotonin transporter gene promoter region polymorphism and stress predicts anxiety symptoms in adolescents: a multi-wave longitudinal study

Objective To explore the interaction between a serotonin transporter gene promoter region polymorphism(5-HTTPR) and stress in predicting anxiety symptoms. Methods Through random cluster sampling, a total of 252 healthy adolescents participated in this study.During the initial assessment, all participants completed the Adolescent Life Events Questionnaire (ALEQ) and Multidimensional Anxiety Scale for Children (MASC) to assess their levels of stress and anxiety and were genotyped for the 5-HTTLPR polymorphism. Participants subsequently completed MASC and ALEQ once every three months during the subsequent 24 months. A multilevel model was used to investigate the interaction between 5-HTTLPR and stress that predict anxiety symptoms. Results The results indicated no major effect of 5-HTTLPR in males (β=0.80, P>0.05)or females(β=-0.21, P>0.05). There were major effects of stress in males(β=0.30, P<0.01) and females (β=0.33, P<0.01)and a significant interaction between 5-HTTLPR and stress. Females with at least one 5-HTTLPR S allele(β=0.11, P<0.01)and males with at least one 5-HTTLPR L allele(β=-0.10, P<0.01)exhibited more anxiety symptoms under stressful situations. Conclusion The interaction between 5-HTTLPR and stress can predict anxiety symptoms in adolescents. There are gender differences on the 5-HTTLPR × stress interaction. Key words: Anxiety symptoms; Serotonin transporter gene promoter region polymorphism; Stress; Adolescent

Association of serotonin transporter gene promoter region polymorphisms with major depressive disorder

Objective To explore the association of serotonin transporter gene promoter region polymorphisms with the onset of major depressive disorder. Methods A case-control association study was taken, 350 patients which met the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-IV) criteria for major depressive disorder (MDD), and 370 age- and gender-matched controls were recruited. HAMD-17 was used to evaluate the severity of depression. Peripheral blood of all the objects was collected, and genomic DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to detect 5-HTTLPR/rs25531 genotypes. SPSS19.0 statistical software was used for statistical analysis. Results The 5-HTTLPR genotypes and alleles frequency distribution between MDD patients (LL, LS, SS genotypes: 10.9%, 38.0%, 51.1%; L, S alleles: 29.9%, 70.1%) and controls (LL, LS, SS genotypes: 12.4%, 40.5%, 47.1%; L, S alleles: 32.7%, 67.3%) had no significant difference (P=0.522; P=0.245). However, the frequency of 5-HTTLPR/rs25531 genotypes and alleles distribution between MDD patients(L’L’, L’S’, S’S’ genotypes: 6.6%, 34.5%, 58.9%; L’, S’ alleles: 21.7%, 78.3%)and controls(L’L’, L’S’, S’S’ genotypes: 8.1%, 42.4%, 49.5%; L’, S’ alleles: 29.3%, 70.7%) had statistically significance(P=0.041; P=0.019). Logistic regression analysis showed that S’S’ (SS, LGS, LGLG) was the risk genotype for MDD (P=0.016, OR=1.461, OR95%CI=1.072-1.991). Conclusion No significant association was found between 5-HTTLPR polymorphism and the onset of major depressive disorder, 5-HTTLPR/rs25531 S’S’ genotype and S’ maybe the risk genes. Key words: Major depressive disorder; Serotonin transporter; Gene polymorphism

Interaction between a serotonin transporter gene promoter region polymorphism and stress predicts depressive symptoms in Chinese adolescents: a multi-wave longitudinal study

BackgroundThe serotonin transporter (5-HTT) gene may play an important role in the onset and development of mental disorders. Past studies have tested whether a functional polymorphism in the 5-HTT gene linked promoter region (5-HTTLPR) moderated the association between stress and depressive symptoms, but the results of these studies were inconsistent. Thus, the aim of the current study was to examine the interaction between 5-HTTLPR and stress that predict depressive symptoms in Chinese adolescents.MethodsA total of 252 healthy adolescents (131 females and 121 males, aged from 14 to 18, mean = 16.00, standard deviation = 0.60) participated in this study. During the initial assessment, all participants completed the Center for Epidemiological Studies Depression Scale (CES-D) and Adolescent Life Events Questionnaire (ALEQ) and were genotyped for the 5-HTTLPR polymorphism. Participants subsequently completed CES-D and ALEQ once every three months during the subsequent 24 months. A multilevel model was used to investigate the 5-HTTLPR × stress interaction in predicting depressive symptoms.ResultsThe results indicated no main effect of 5-HTTLPR and a significant 5-HTTLPR × stress interaction in females only. Females with at least one 5-HTTLPR S allele exhibited more depressive symptoms under stressful situations. No significant 5-HTTLPR × stress interaction was found in males.ConclusionsIn Chinese adolescents, there are gender differences on the interaction between 5-HTTLPR and stress that predict depressive symptoms. The association between stress and depressive symptoms is moderated by 5-HTTLPR in Chinese female adolescents.

Serotonin transporter gene promoter region polymorphisms and serotonin transporter expression in the colonic mucosa of irritable bowel syndrome patients

The role of serotonin transporter (SERT) gene polymorphism in irritable bowel syndrome (IBS) has been demonstrated. However, the expression of SERT mRNA and proteins in the colonic mucosa with different 5-HTT gene-linked polymorphic region (5-HTTLPR) genotypes remains unknown. We examined SERT mRNA and protein levels in colon biopsies from patients with different 5-HTTLPR genotypes and evaluated the links between the polymorphism and the expression levels. Two hundred and fifty-four patients with IBS and 120 healthy subjects were studied. DNA samples were extracted from peripheral blood and genotyped by polymerase chain reaction (PCR). SERT mRNA and protein levels were evaluated by quantitative real time PCR and western blotting. The promoter efficiency of the serotonin transporter promoter (SERT-P) was evaluated with luciferase reporter system. The frequency of the L/L genotype in C-IBS group was significantly higher than that in the control and D-IBS. However, the S/S genotype in D-IBS was significantly higher than that in C-IBS. The transcriptional efficiency of the L/L genotype was significantly higher than that in the L/S and S/S genotype. Patients with the L/L genotype demonstrated increased production of the SERT protein when compared with L/S and S/S patients. The l variant increased SERT promoter activity by 2.43-fold when compared with the s variant. Polymorphism in the promoter region of the SERT gene can influence the expression of SERT mRNA and the levels of the SERT protein in the colonic mucosa, thereby playing a key role in motility-related symptoms of IBS patients.

The relationship between serotonin transporter gene promoter polymorphism and serum lipid levels at young age in a longitudinal population-representative study

The serotonin transporter gene promoter region polymorphism (5-HTTLPR) has been linked to psychiatric disorders, mostly anxiety and affective disorders. In elderly populations 5-HTTLPR polymorphism has also been reported to be associated with serum lipid levels. We have examined the interaction of the 5-HTTLPR polymorphism and the markers of lipid metabolism at young age in a longitudinal, population-representative cohort study. The sample of the Estonian Children Personality Behaviour and Health Study (initially cohorts of 9 and 15 year old children, complete lipid and genotype data for n=1176) was examined throughout 10 years. Subjects were genotyped and the levels of low-density lipoproteins, high-density lipoproteins, triglycerides, and total cholesterol were measured. Children and adolescents carrying the s allele of the 5-HTTLPR polymorphism had lower levels of low-density lipoprotein and total cholesterol. At the age of 25, the s allele carriers had higher levels of high-density lipoproteins. These associations were independent of gender. Thus the 5-HTTLPR can be associated with the serum lipid levels and in particular low-density lipoproteins already in a young age.

Serotonin transporter gene promoter region polymorphism and selective processing of emotional images

Several studies have now documented that the serotonin transporter promoter region (5-HTTLPR) polymorphism predicts neural response to affective images in brain regions involved in the experience of emotion. However, the behavioral consequences of this genetic effect are less well known. The current study used eye-tracking methodology to examine how individuals genotyped for the 5-HTTLPR allocated their attention when simultaneously presented an array of positive and negative emotional scenes. Short 5-HTTLPR allele homozygotes displayed a bias to focus on positive images, particularly in the first half of the 30s trial. In contrast, long 5-HTTLPR allele homozygotes viewed the stimuli in a more evenhanded fashion. Thus, short 5-HTTLPR allele homozygotes may be attempting to regulate greater reactivity to negative stimuli by purposefully turning their attention towards positive stimuli. Although this sensitivity may have benefits under benign conditions, it may also increase vulnerability to affective disorders when cognitive resources needed to turn attention away from negative stimuli are compromised.

Lack of association of the serotonin transporter gene promoter region polymorphism, 5‐HTTLPR, including rs25531 with cigarette smoking and alcohol consumption

We addressed the question whether 5-HTTLPR, a variable number of tandem repeats located in the 5' end of the serotonin transporter gene, is associated with smoking or alcohol consumption. Samples of DNA from 1,365 elderly women with a mean age of 69.2 years were genotyped for this polymorphism using a procedure, which allowed the simultaneous determination of variation in the number of repeat units and single nucleotide changes, including the A > G variation at rs25531 for discrimination between the L(A) and L(G) alleles. Qualitative and quantitative information on the women's current and previous consumption of cigarettes and alcohol were obtained using a questionnaire. Genotypes were classified according to allele size, that is, S and L with 14 and 16 repeat units, respectively, and on a functional basis by amalgamation of the L(G) and S alleles. Data were subjected to regression analyses. These analyses revealed P values for associations between 5-HTTLPR genotype and alcohol and cigarette consumption in the range from 0.15 to 0.92. On adjustment for age and educational level, significance for the associations of 5-HTTLPR with the smoking and alcohol consumption measures was not reached. We conclude that 5-HTTLPR is not an important determinant of smoking behavior and alcohol consumption in elderly women.

Serotonin transporter gene polymorphism and treatment response to serotonin reuptake inhibitor (escitalopram) in depression: An open pilot study

Background:Blocking of the serotonin transporter is the main mechanism of action of SSRIs; therefore, the gene encoding this protein is a strong candidate for a possible genetic influence on the treatment response.Aim:To evaluate relationship between serotonin transporter gene promoter region polymorphism and the efficacy of SSRI (escitalopram) treatment in depression.Materials and Methods:Fifty-seven consecutive patients with unipolar depressive episode (DSM IV criteria) were genotyped for the SERT gene polymorphism and treated with escitalopram 20 mg/day. Weekly assessment (HAM-D-21) was made for treatment response up to 6 weeks.Results:Significant (P > 0.0001) difference between groups (ll vs. ss or ls) in response to treatment by escitalopram was revealed by our study. However, no difference with respect to age, gender, or onset of illness was observed between genotype subgroups.Conclusion:The study suggests that serotonin transporter gene polymorphism may have an influence on the effectiveness of SSRI treatment in depressive disorders, irrespective of clinical variables. Further controlled studies are required to validate these results

Platelet MAO activity and the 5-HTT gene promoter polymorphism are associated with impulsivity and cognitive style in visual information processing

Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning. The effect of the two markers for serotonin system efficiency on performance in a visual comparison task (VCT) and self-reported impulsiveness (Barratt Impulsiveness Scale, BIS-11) were investigated in healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study. Possible confounding effect of general cognitive abilities on the performance in VCT was controlled for. Low platelet MAO activity and carrying of the S allele of 5-HTTLPR were both associated with higher error-rate and more impulsive performance in VCT. Platelet MAO activity and 5-HTTLPR S allele had a significant interactive effect on self-reported impulsivity (BIS-11). The effect of platelet MAO activity on both self-reported and performance impulsivity was significant only in the S allele carriers. The effect of 5-HTTLPR S allele on impulsive performance remained significant after controlling for general cognitive abilities. The two markers of lower serotonergic capacity, 5-HTTLPR S allele and low platelet MAO activity, have a similar and partly synergistic influence on self-reported as well as performance measures of impulsivity.

Serotonin Transporter Gene Promoter Region Polymorphism Associated With Poststroke Major Depression

The authors examined variations of serotonin transporter-linked promoter region (5-HTTLPR) functional polymorphism in 26 stroke patients with major depression and in 25 unrelated nondepressed stroke subjects of Caucasian descent. Findings indicate a significant association between 5-HTTLPR short variant genotype and poststroke major depression.

Serotonin Transporter Gene Promoter Region Polymorphism Associated With Poststroke Major Depression

The authors examined variations of serotonin transporter-linked promoter region (5-HTTLPR) functional polymorphism in 26 stroke patients with major depression and in 25 unrelated nondepressed stroke subjects of Caucasian descent. Findings indicate a significant association between 5-HTTLPR short variant genotype and poststroke major depression.

Clinical Efficacy of Fluvoxamine and Functional Polymorphism in a Serotonin Transporter Gene on Childhood Autism

We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment. 5-HTTLPR (long (l) or short(s)), was analyzed by the PCR method. Ten out of 18 patients responded to fluvoxamine treatment; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele. However, with respect to language use, a significant effectiveness was noted in the s allele. 5-HTTLPR may influence the individual responses to fluvoxamine administration.

P.7.014 An association study of the impulsiveness and aggressiveness in adolescent prisoners with serotonin transporter gene promoter region polymorphism

P.7.014 An association study of the impulsiveness and aggressiveness in adolescent prisoners with serotonin transporter gene promoter region polymorphism

Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.