Gene-linked Polymorphic Region Research Articles

Interaction of 5-HTTLPR and SLE disease status on resting-state brain function

BackgroundNeuropsychiatric involvement in systemic lupus erythematosus (SLE) is a common clinical manifestation. In SLE patients, cerebral function is a more sensitive predictor of central nervous system damage, and abnormalities in cerebral function may be apparent before substantial neuropsychiatric symptoms occur. The 5-hydroxynyptamine(5-HT) system has the ability to interact with the majority of the neurochemical systems in the central nervous system (CNS), influencing brain function. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) is an essential element of the 5-HT system gene polymorphism and is directly related to the control of 5-hydroxytryptamine transporter (5-HTT)gene expression. The relationship between 5-HTTLPR and functional brain measurements in SLE patients requires more investigation because it is one of the most attractive imaging genetics targets for shedding light on the pathophysiology of neuropsychiatric lupus.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) images were collected from 51 SLE patients without obvious neuropsychiatric manifestations and 44 healthy volunteers. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) were selected as indicators for evaluating brain function. In accordance with the Anatomical Automatic Labeling template, the gray matter was divided into 116 regions. The mean ReHo value, mean ALFF value, and mean fALFF value of each brain region were extracted. 5-HTTLPR genotypes of all research objects were tested by polymerase chain reaction and agarose gel electrophoresis. Two-way analysis of covariance was used to investigate whether there is an interaction effect between SLE disease status and 5-HTTLPR genotype on resting-state brain function.ResultsIn SLE patients with S/S homozygosity, there were notably lower mean ReHo, mean ALFF, and mean fALFF values observed in the right parietal, inferior angular gyrus, and the right paracentral lobule compared to healthy controls. However, this distinction was not evident among carriers of the L allele. Within the S/S genotype, SLE patients exhibited decreased mean ReHo in the left posterior cingulate gyrus, reduced mean fALFF in the left caudate nucleus, and diminished mean ALFF in the left temporal pole: superior temporal gyrus, in contrast to the HC group. Conversely, no such differences were discerned among carriers of the L allele. Notably, among L allele carriers, SLE patients displayed a higher mean ReHo value in the right hippocampus compared to the HC group, while demonstrating a lower mean ALFF value in the left medial and paracingulate gyrus in contrast to the HC group. Conversely, these differences were not apparent among S/S homozygotes.ConclusionsBrain function in the right parietal and inferior angular gyrus and the right paracentral lobule is affected by the interaction effect of SLE disease status and 5-HTTLPR genotype.

Meta-Analysis of the Association Between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region and Functional Dyspepsia and its Subtypes.

Background: Association studies of variations in the 5-hydroxytryptamine (5-HT, serotonin) transporter gene-linked polymorphic region (5-HTTLPR) and functional dyspepsia (FD) have yielded contradictory results. Hence, we performed a meta-analysis to clarify inconsistencies between the 5-HTTLPR polymorphism with FD and it subtypes. Methods: We performed a literature search in PubMed, Embase, Web of Science, Cochrane Library, and CNKI, including articles published until March 2022. We calculated and pooled odds ratios (ORs) with their 95% confidence intervals (CIs) in Stata 15.0. Data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. Results: The meta-analysis included six studies, comprising 488 cases and 1513 healthy controls. We did not observe a significant association between the 5-HTTLPR polymorphism and FD in the overall population. In subgroup analyses, the 5-HTTLPR polymorphism was significantly associated with FD-subtype epigastric pain syndrome (EPS) (SS vs. LL+LS, OR = 0.620, 95% CI: 0.414-0.930; SS vs. LS, OR = 0.640, 95% CI: 0.417-0.980; S vs. L, OR = 0.655, 95% CI: 0.471-0.911). However, no association was observed with the other subtype, postprandial distress syndrome (PDS). Conclusion: While the 5-HTTLPR polymorphism had no relationship with FD overall, splitting the disease into its subtypes revealed a clear association with EPS.

Correlation between 5-HTTLPR gene polymorphism and cognitive function of traumatic stress in Chinese Han children.

BackgroundPost-traumatic stress disorder (PTSD) is a trauma-related psychological disorder with serious social and familial impacts. The involvement of 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) in numerous mental disorders has been documented. This study explored the correlation between 5-HTTLPR gene polymorphism and cognitive function in Chinese Han children with PTSD.MethodsA total of 60 PTSD children treated from December 2019 to December 2021 were selected as study participants, with another 60 healthy children selected as controls. We assessed the cognitive function of participants using the Mini-Mental State Examination (MMSE). Additionally, the PTSD level was estimated by the Children’s Revised Impact of Event Scale (CRIES). The 5-HTTLPR gene polymorphism was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The genotype and allele frequency were evaluated via case-control association analysis.ResultsChildren in the PTSD group showed low MMSE scores and high CRIES scores. In terms of genotype, cases of LL, LS, and SS in PTSD children were 4 (6.67%), 20 (33.3%), and 36 (60.00%), and 18 (30.00%), 28 (46.67%), and 14 (23.33%) cases in healthy controls. In terms of allele gene frequency, incidences of L and S were 23.33% and 76.67% in PTSD children, respectively, and were 53.33% and 46.67% in healthy controls, respectively. Moreover, the CRIES and MMSE scores of LS and SS genotypes were evidently different from those of LL genotype in PTSD children.ConclusionsPolymorphism of the 5-HTTLPR gene is correlated with cognitive dysfunction in Chinese Han children with PTSD.

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Role of the cAMP–PKA–CREB–BDNF pathway in abnormal behaviours of serotonin transporter knockout mice

Serotonin transporter gene-linked polymorphic region polymorphisms are associated with anxiety, neuroticism, affective disorders and vulnerability to stressful life events; however, the relevant physiological mechanisms are not well understood. Serotonin transporter knockout mice have been widely used as a model of allelic variation of serotonin transporter function in humans; herein, wild-type mice and heterozygous and homozygous knockout mice models were established to explore the behavioural changes related to different genotypes and the possible physiological mechanisms. Behavioural changes were assessed using behavioural tests, namely, elevated plus maze, open field, Morris water maze and rotarod tests. Serum indicators were detected using the enzyme-linked immunosorbent assay. Compared with wild-type mice, homozygous mice showed significant anxiety-like behaviours in the plus maze and open field tests; conversely, anxiety-like behaviours in heterozygous mice were less pronounced. Homozygous mice also showed cognitive impairment and motor inhibition in the Morris water maze and rotarod tests. Serotonin levels decreased in both heterozygous and homozygous mice, and 5-hydroxytryptophan, protein kinase A, adenylyl cyclase, cyclic adenosine monophosphate response element-binding protein and brain-derived neurotrophic factor levels were lower in homozygous mice than in wild-type and heterozygous mice, whereas no statistical differences were found between wild-type and heterozygous mice. Additionally, there was a correlation between serological and behavioural indicators. This study provided experimental evidence that the cyclic adenosine monophosphate–protein kinase A–cyclic adenosine monophosphate response element-binding protein–brain-derived neurotrophic factor pathway may be involved in the regulation of polymorphism to stress and enriched the behavioural and physiological characteristics of serotonin transporter knockout mice.

Serotonin Transporter Gene Polymorphism in Patients with Schizophrenic Disorders

Objective: Studies performed to solve the genetic basis of schizophrenia have focused on the role of serotonin in the etiology of schizophrenia and the function of serotonin transporter gene. This study aimed to investigate whether there was a relationship between schizophrenia and polymorphism of the Variable Number of Tandem Repeats (VTNR) and 5-HTT Gene-Linked Polymorphic Region (5-HTTLPR) variants in the transcriptional control region of the serotonin transporter gene or not.Method: A total of 55 schizophrenia patients who were diagnosed according to the diagnostic criteria of DSM-IV-TR and 32 healthy volunteers (the control group) were included in the study. DNAs were extracted from the bloods collected from the patient and control groups with the salting-out method. Alleles of the serotonin transporter gene polymorphism were determined with the polymerase chain reaction (PCR) method.Results: Based on the serotonin transporter gene intron 2 VNTR polymorphism, the distribution of 12/12, 12/10, 10/10, and 12/9 genotypes was 47.3%, 47.3%, 3.6%, and 1.8% in the patients and 46.9%, 46.9% and 6.3% respectively in the control group. There was no 12/9 genotype in the control group. The distribution of L/L, L/S and S/S genotypes according to the 5-HTTLPR polymorphism was 30.9%, 41.8% and 27.3% in the patients and 28.1%, 50.0% and 21.9% respectively in the control group. Conclusion: Although the allele and genotype distributions of the serotonin transporter gene polymorphism relatively differed between the patient and control groups this difference was not statistically significant.

A comprehensive assessment of genetic variation in serotonin transporter gene (5-HTTLPR+rs25531) and the response to dapoxetine in Chinese patients with premature ejaculation.

This study was to explore whether serotonin transporter gene-linked polymorphic region polymorphisms (5-HTTLPR+rs25531) influence the response to dapoxetine treatment in a Chinese population with premature ejaculation (PE). 112 patients with PE re-enrolled from our previous study received dapoxetine monotherapy. At the endpoint, patients with S'S' had a significant increased risk of nonresponse compared with L' carriers (p<.001). The improvement in S'S' genotype was significantly lower in premature ejaculation profile (PEP) items of 'control over ejaculation' (p=.035) and 'distress related to ejaculation' (p=.017) than that in L' carriers. As to clinical global impression of change (CGIC), results in S'S' subjects showed significantly lower scores (p=.008) and a less satisfaction rate reporting at least 'better' (p=.020) compared with L' carriers. Moreover, our findings suggested that patients with S'S' were more likely to develop adverse effects (AEs) compared with L' carriers (p=.040). This study suggests that PE patients bearing the S'S' genotype have an inferior comprehensive efficacy and safety of dapoxetine treatment, which consist of poorer response in IELTs, less improvement in patient-reported outcome (PRO) measures and greater incidence of AEs, than L' carriers. Variants of triallelic 5-HTTLPR may play a major role as a predictor of treatment response to dapoxetine.

Post-traumatic Stress Symptoms and Serotonin Transporter (5-HTTLPR) Polymorphism in Breast Cancer Patients.

Introduction: Post-traumatic Symptoms (PTSS) and Post-traumatic Stress Disorder (PTSD) have been reported to affect a quite significant proportion of cancer patients. No study has examined the relationship between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cancer, including Gene-Environment interactions between this polymorphism and specific causes of distress, such as cancer related problems (CRP) or life stressful events (SLE).Methods: One hundred and forty five breast cancer outpatients participated in the study and were assessed using the Impact of Event Scale (IES), the Problem List (PL) developed by the National Comprehensive Cancer Network (NCCN) Distress Management Guidelines and the Paykel's Life Events Interview to evaluate the exposure to SLE during the year before the cancer diagnosis. Each patient was genotyped for 5-HTTLPR polymorphism by analyzing genomic DNA obtained from whole blood cells. Gene-Environment interactions were tested through moderation analysis.Results: Twenty-six patients (17.7%) were classified as PTSS cases using the IES. Genotype and phenotype distributions did not differ across individuals with/without PTSS (genotype: χ2 = 1.5; df = 2; p = 0.3; phenotype χ2 = 0.9; df = 1; p = 0.2). For both the genotype and phenotype model, using CRP as a predictor showed significant gene-environment interactions with IES total score (p = 0.020 and p = 0.004, respectively), with individuals carrying the l/l allele showing a greater probability of experiencing PTSS. No interaction was found in relationship to SLE (p = 0.750).Conclusion: This study showed a significant GEI between CRP and PTSS in breast cancer patients, with carriers of the l/l allele showing indicators consistent with greater sensitivity to stress.

Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating shen and strengthening spleen

To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating shen and strengthening spleen and pinaverium bromide, and explore the relevant mechanism of curative effect of acupuncture in view of polymorphism of 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR). A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating shen and strengthening spleen, i.e. Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37) and Zusanli (ST 36), etc. The treatment was given once every 2 days, 3 times a week. In the western medication group, pinaverium bromide was prescribed for oral administration, 50 mg each time, 3 times daily. The duration of treatment was 6 weeks in each group. Separately, before treatment, after treatment and in 3-month follow-up, the IBS symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) scores were adopted in assessment. After treatment, the curative effect and safety were compared between the two groups. Before treatment, 5-HTTLPR genotypes were determined in the patients. After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (P<0.01) and the scores in the acupuncture group were lower than those in the western medication group (P<0.01). After treatment and in follow-up, the total scores of IBS-QOL in the two groups were all increased as compared with those before treatment (P<0.01) and the score in the acupuncture group was higher than the western medication group in follow-up (P<0.01). The total effective rate was 79.2% (122/154) in the acupuncture group, higher than 58.4% (45/77) in the western medication group (P<0.01). There was no severe adverse reaction found in the two groups. The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes was greater than that in the patients with LL in the acupuncture group (P<0.01). The difference in the total score of ISB-SSS before and after treatment in the patients with SS genotype was greater than that in the patients with LL in the western medication group (P<0.01). The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes in the acupuncture group was greater than that in the patients with the same genotypes in the western medication group (P<0.01). Acupuncture for regulating shen and strengthening spleen achieves the more curative effect on IBS-D as compared with pinaverium bromide. The acupuncture regimen effectively relieves the clinical symptoms and improves the quality of life in patients as well as presents a satisfactory long-term effect and safety. The clinical curative effect of acupuncture is correlated with 5-HTTLPR polymorphism, in which, the curative effect of acupuncture may be more effective in the patients with LS and SS genotypes.

The Mediating Effect of Psychological Distress on the Association between BDNF, 5-HTTLPR, and Tinnitus Severity

ObjectiveTo investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association. MethodsEighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping. ResultsNo significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus. ConclusionOur findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5-HTTLPR Genotype Dependent in Older Adults.

Depressive symptoms are diagnosed by physicians using scales but their pathophysiology is unclear. Low serotonin (5-HT) levels play an important role in depression, and the 5-HT transporter (5-HTT) is an important regulator of plasma serotonin levels and reuptake. Additionally, the 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with depression. The aim was to clarify the roles of plasma serotonin levels in plasma and the 5HTTPLR polymorphism in depressive symptoms in older adults. A total of 84 older adult participants were evaluated. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale of 20 items (CESD-20). The plasma serotonin levels were determined by ELISA, and the 5-HTTLPR genotype was analyzed by PCR. Depressive symptoms were present in 39.3% (N = 33) of the participants. The median plasma serotonin level was 204.34 ng/mL (SD = 93.88). A significant correlation was found between the CESD-20 scale and plasma serotonin levels (r = -.256; p = .019). Low serotonin levels were associated with the presence of depressive symptoms (p = .001). The 5-HTTLPR analysis showed that of the 84 older adults, 35.7% had the SS genotype, 10.7% had the LL genotype, and 53.6% were heterozygous. The 5-HTTLPR polymorphism was not associated with depressive symptoms (p = .587) and plasma serotonin levels (p = 0.391). Depressive symptoms correlate with low serotonin levels in plasma, but not with the 5-HTTLPR polymorphism in older Mexican adults.

The role of the 5-HTTLPR polymorphism in acquired capability for suicide.

According to the Interpersonal Psychological Theory of Suicide, capability for suicide comprises two dimensions: fearlessness about death and elevated pain tolerance. The short (S) allelic variant of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) has repeatedly been associated with more violent and lethal suicide methods and lethality of suicide attempts. The current study aimed to investigate whether 5-HTTLPR allelic variants are associated with fearlessness about death and pain tolerance/persistence and whether it moderates the relationship between childhood maltreatment and acquired capability for suicide. A cohort of 208 inpatients hospitalized due to a recent suicide attempt or severe suicidal ideation was genotyped for the 5-HTTLPR and assessed for childhood maltreatment. Subjective pain tolerance and fearlessness about death as well as objective pain persistence was assessed using a pressure algometer. Fearlessness about death, pain tolerance, and pain persistence did not differ between 5-HTTLPR genotypes. However, there was a significant correlation between self-reported childhood maltreatment and fearlessness about death that emerged exclusively in homozygous S-allele carriers. Results suggest that there are no "high-risk"-alleles that generally increase capability for suicide. However, in terms of future suicide-related behaviors exposure to childhood maltreatment events could exert a particularly negative influence on homozygous S-allele carriers by increasing their fearlessness about death.

5-HTTLPR polymorphism and depression risk in Parkinson's disease: an updated meta-analysis.

The relationship between the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and depression in Parkinson's disease (PD) has remained controversial. Therefore, we conducted this meta-analysis to evaluate the relationship between 5-HTTLPR polymorphisms and depression in PD. Relevant online databases were searched for cross-sectional, case-control or cohort studies examining relations between 5-HTTLPR polymorphisms (S/L) and the risk of developing depression of PD using a meta-analysis. Odd ratios (ORs) of 5-HTTLPR polymorphisms (S/L allele genotype) were calculated between depression in PD and PD for each study. Five observational studies were identified. Overall ORs for 5-HTTLPR S-Allele genotype was 1.98 (95% CI 0.92-4.26) in the dominant model, 1.43 (95% CI 1.08-1.90) in the recessive model, 2.64 (95% CI 1.01-6.88) in the additive model, independently. The overall ORs of S-Allele genotype was 1.51 (95% CI 0.63-3.64) for the Caucasian subgroup, and 1.44 (95% CI 1.05-1.98) for the non-Caucasian subgroup in the recessive model. This meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) is correlated with an increased depression risk in PD, and this highlights the needs for these people to take some effective approaches (if any) in prevention of depression of PD before its onset.

The important effect of 5-HTTLPR polymorphism on the risk of depression in patients with coronary heart disease: a meta-analysis

BackgroundDepression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However, the potential pathophysiological mechanisms remain unknown. It might be influenced by genetic and environmental factors. According to recent researches, there is potential association between serotonin transporter gene-linked polymorphic region (5-HTTLPR) polymorphism and risk of depression in CHD patients, but the results are still inconclusive. Therefore, we performed this meta-analysis based on unadjusted and adjusted data to ascertain a more precise conclusion.MethodsWe searched relevant articles through PubMed, Embase, Web of Science, Chinese BioMedical Literature (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases up to August 26, 2019. Study selection and data extraction were accomplished by two authors independently. The strength of the correlation was assessed via odds ratios (ORs) with their 95% confidence intervals (95%CIs).ResultsThis meta-analysis enrolled six observational studies. Based on unadjusted data, there was significant relationship between 5-HTTLPR polymorphism and depression risk in CHD patients under all genetic models (S vs. L: OR = 1.31, 95%CI = 1.07–1.60; SS vs. LL: OR = 1.73, 95%CI = 1.12–2.67; LS vs. LL: OR = 1.47, 95%CI = 1.13–1.92; LS + SS vs. LL: OR = 1.62, 95%CI = 1.25–2.09; SS vs. LL + LS: OR = 1.33, 95%CI = 1.02–1.74). The results of adjusted data further strengthened this relationship (SS vs. LL: OR = 1.89, 95%CI = 1.28–2.80; LS vs. LL: OR = 1.69, 95%CI = 1.14–2.51; LS + SS vs. LL: OR = 1.80, 95%CI = 1.25–2.59). Subgroup analyses based on ethnicity and major depressive disorder revealed similar results to that of the overall analysis. No evidence of publication bias was observed.ConclusionsOur results suggest that 5-HTTLPR polymorphism may have an important effect on the risk of depression among patients with CHD, and carriers of the S allele of 5-HTTLPR are more vulnerable to depression.

The association between childhood maltreatment and empathic perspective taking is moderated by the 5-HTT linked polymorphic region: Another example of "differential susceptibility".

Previous research has suggested that the short (S)-allele of the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) may confer "differential susceptibility" to environmental impact with regard to the expression of personality traits, depressivity and impulsivity. However, little is known about the role of 5-HTTLPR concerning the association between childhood adversity and empathy. Here, we analyzed samples of 137 healthy participants and 142 individuals diagnosed with borderline personality disorder (BPD) focusing on the 5-HTTLPR genotype (S/L-carrier) and A/G SNP (rs25531), in relation to childhood maltreatment and empathy traits. Whereas no between-group difference in 5-HTTLPR genotype distribution emerged, the S-allele selectively moderated the impact of childhood maltreatment on empathic perspective taking, whereby low scores in childhood trauma were associated with superior perspective taking. In contrast, L-homozygotes seemed to be largely unresponsive to variation in environmental conditions in relation to empathy, suggesting that the S-allele confers "differential susceptibility". Moreover, a moderation analysis and tests for differential susceptibility yielded similar results when transcriptional activity of the serotonin transporter gene was taken into account. In conclusion, our findings suggest that the S-allele of the 5-HTTLPR is responsive to early developmental contingencies for "better and worse", i.e. conferring genetic plasticity, especially with regard to processes involving emotional resonance.

Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).

Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI). The triallelic and biallelic classification of the 5-HTTLPR polymorphism were genotyped from buccal swabs.Multivariate logistic regression models were used to predict PTSD, including interaction terms to explore gene-environment (G x E) interactions. The vast majority (83%, n = 341) of the Lorca survey respondents (n = 412, 71% response rate) were genotyped. Both classifications of the 5-HTTLPR genotype were in Hardy-Weinberg equilibrium. Prior lifetime PTSD was the only variable that remained a significant predictor after adjustments. There were no significant main effects of earthquake related stressors or 5-HTTLPR. However, G x E interactions of 5-HTTLPR with high emotional impact and prior lifetime anxiety disorders were statistically significant. These results provide new evidence of the modulation effect of the 5-HTTLPR polymorphisms on PTSD risk. This information might characterize people at higher risk of developing PTSD after an earthquake exposure.

Post‐traumatic stress symptoms of children and adolescents exposed to the 2008 Wenchuan Earthquake: A longitudinal study of 5‐HTTLPR genotype main effects and gene–environment interactions

Experiencing disasters causes severe mental disorders, among which post-traumatic stress disorder (PTSD) is the most common. We conducted a longitudinal study to examine the effect of 5-hydroxyl tryptamine transporter gene-linked polymorphic region (5-HTTLPR) genotype on child and adolescent PTSD symptom course after the 2008 Wenchuan Earthquake. We genotyped 963 participants who personally experienced the earthquake. PTSD symptoms were measured by University of California, Los Angeles PTSD reaction index at 2.5, 3.5, 4.5 and 5.5 years after the earthquake, respectively. Latent growth model was utilised to examine the main effect and gene-environment interaction effect of 5-HTTLPR on PTSD's symptom course. 5-HTTLPR genotype predicted initial PTSD symptom severity (β=0.108, p=.019) and rates of symptom recovery (β=-0.120, p=.031) between 2.5 and 5.5 years. Compared with L' allele carriers, those with S'S' genotype showed higher initial symptom severity but also faster recovery rate. 5-HTTLPR genotype only predicted symptom severity at 2.5 years after the earthquake, after controlling for sex, age, ethnicity and trauma severity (β=0.108, p=.019). This is the first evidence of the effect of 5-HTTLPR genotype on child and adolescent PTSD symptoms longitudinally, offering a novel perspective on the effect of 5-HTTLPR on PTSD symptom development following trauma exposure.

Association between polymorphisms in the serotonin transporter gene-linked polymorphic region and risk for irritable bowel syndrome in China: evidence based on a meta-analysis.

ObjectiveThe association between mutations in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and irritable bowel syndrome (IBS) differs between populations. This meta-analysis was designed to assess the relationship between 5-HTTLPR polymorphisms and IBS in a Chinese population.MethodsRelevant published studies from PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure databases were accessed prior to May 2018. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using STATA software.ResultsA total of 754 IBS cases and 578 healthy controls in six studies were included in this meta-analysis. Significant results were obtained between 5-HTTLPR polymorphisms and IBS risk among studies with the genotype distribution of controls in Hardy–Weinberg equilibrium (L vs. S, OR = 1.41, 95% CI: 1.11–1.79; LL vs. SS, OR = 2.17, 95% CI: 1.16–4.08; LL vs. LS + SS, OR = 2.29, 95% CI: 1.25–4.20). In subgroup analyses, 5-HTTLPR polymorphisms were significantly associated with increased IBS-C risk in China; however, no risk was observed for IBS-D and IBS-M.ConclusionThis meta-analysis clearly indicates that 5-HTTLPR polymorphisms are associated with an increased risk of IBS in the Chinese population, especially IBS-C.

Association of DRD2, 5-HTTLPR, and 5-HTTVNTR Gene Polymorphisms With Posttraumatic Stress Disorder in Tibetan Adolescents: A Case-Control Study.

Earthquake exposure is a source of stress, yet only a minority of survivors experience clinically meaningful disturbance in psychological function. Genetic epidemiological research has found that posttraumatic stress disorder (PTSD) symptoms are associated with genetic factors. Further research to reveal which genetic loci relate to the development of PTSD is warranted. We investigated the relationships between PTSD and the dopamine D2 receptor ( DRD2) gene Taq I polymorphism and the serotonin transporter gene ( SCL6A4) polymorphisms 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and 5-HTTVNTR in 565 adolescent earthquake survivors. PTSD-positive adolescents were identified using the PTSD Checklist-Civilian Version and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 4. Genotypes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism analysis. The Pearson χ2 test was used to investigate the differences in genotype and allele frequencies between case and control groups. Binary logistic regression analysis was performed to identify possible influencing factors for PTSD. The DRD2 Taq I and 5-HTTVNTR polymorphisms had statistically significant effects on PTSD, while 5-HTTLPR did not. Specifically, the DRD2 Taq I A1 allele was highly positively correlated with PTSD, whereas the 10 allele of 5-HTTVNTR was negatively correlated. These data suggest that the DRD2 Taq I and 5-HTTVNTR genotypes moderate sensitivity to stress and the expression of emotional disturbance involving PTSD symptoms. These findings have important implications for PTSD etiology as well as for both primary prevention and treatment strategies.

Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer\u2019s disease

BackgroundSerotoninergic pathways underlying delusion symptoms in Alzheimer’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription.MethodsWe investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer’s Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory.ResultsDelusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121–0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522–0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195–4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD.ConclusionsMore studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.