Dataset Information

Lack of Association Between Serotonin Transporter Gene (SLC6A4) Promoter Methylation and Amygdala Response During Negative Emotion Processing in Individuals With Alcohol Dependence.

ABSTRACT: AIMS:Differences in DNA methylation of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression and predict brain functions in healthy individuals. This study investigated the association between SLC6A4 promoter methylation and threat-related amygdala activation in individuals with alcohol dependence (AD). METHODS:Methylation of the SLC6A4 promoter region was assessed using peripheral blood DNA from 45 individuals with AD and 45 healthy controls (HCs). All participants completed an emotional face matching task in a 3-T magnetic resonance imaging (MRI) scanner. RESULTS:Results did not reveal any association between SLC6A4 promoter methylation variation and threat-related amygdala activation in HCs or individuals with AD. Furthermore, methylation in the promoter region of SLC6A4 did not significantly differ between the groups. CONCLUSIONS:Our results do not replicate a previous finding that increased methylation in the promoter region of SLC6A4 is associated with threat-related amygdala activation in healthy individuals and further show that there is no such association in individuals with AD. Given that the number of imaging epigenetics studies on SLC6A4 is very limited to date, these inconsistent results indicate that future research is needed to clarify its association with amygdala reactivity in both healthy and clinical populations.

SUBMITTER: Muench C

PROVIDER: S-EPMC6516430 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Lack of Association Between Serotonin Transporter Gene (SLC6A4) Promoter Methylation and Amygdala Response During Negative Emotion Processing in Individuals With Alcohol Dependence.

Muench Christine C Luo Audrey A Charlet Katrin K Lee Jisoo J Rosoff Daniel B DB Sun Hui H Fede Samantha J SJ Jung Jeesun J Momenan Reza R Lohoff Falk W FW

Alcohol and alcoholism (Oxford, Oxfordshire) 20190501 3

<h4>Aims</h4>Differences in DNA methylation of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression and predict brain functions in healthy individuals. This study investigated the association between SLC6A4 promoter methylation and threat-related amygdala activation in individuals with alcohol dependence (AD).<h4>Methods</h4>Methylation of the SLC6A4 promoter region was assessed using peripheral blood DNA from 45 individuals with AD and 45 healthy controls (HCs). Al ...[more]

PMID: 31008507

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Project description:Panic disorder (PD) and social anxiety disorder (SAD) are moderately heritable anxiety disorders. We analyzed five genes, derived from pharmacological or translational mouse models, in a new case-control study of PD and SAD in European Americans: (1) the serotonin transporter (SLC6A4), (2) the serotonin receptor 1A, (3) catechol-O-methyltransferase, (4) a regulator of g-protein signaling and (5) the gastrin-releasing peptide receptor. Cases were interviewed using the schedule for affective disorders and schizophrenia and were required to have a probable or definite lifetime diagnosis of PD (N=179), SAD (161) or both (140), with first onset by age 31 and a family history of anxiety. Final diagnoses were determined using the best estimate procedure, blind to genotyping data. Controls were obtained from the National Institute of Mental Health Human Genetics Initiative; only subjects above 25 years of age who screened negative for all psychiatric symptoms were included (N=470). A total of 45 single nucleotide polymorphisms were successfully genotyped over the five selected genes using Applied Biosystems SNPlex protocol. SLC6A4 provided strong and consistent evidence of association with the PD and PD+SAD groups, with the most significant association in both groups being at rs140701 (chi(2)=10.72, P=0.001 with PD and chi(2)=8.59, P=0.003 in the PD+SAD group). This association remained significant after multiple test correction. Those carrying at least one copy of the haplotype A-A-G constructed from rs3794808, rs140701 and rs4583306 have 1.7 times the odds of PD than those without the haplotype (95% confidence interval: 1.2-2.3). The SAD only group did not provide evidence of association, suggesting a PD-driven association. The findings remained after adjustment for age and sex, and there was no evidence that the association was due to population stratification. The promoter region of the gene, 5-HTTLPR, did not provide any evidence of association, regardless of whether analyzed as a triallelic or biallelic locus, nor did any of the other four candidate genes tested. Our findings suggest that the serotonin transporter gene may play a role in PD; however, the findings require replication. Future studies should attend to the entire genetic region rather than the promoter.

Dataset Information

Lack of Association Between Serotonin Transporter Gene (SLC6A4) Promoter Methylation and Amygdala Response During Negative Emotion Processing in Individuals With Alcohol Dependence.

Publications

Lack of Association Between Serotonin Transporter Gene (SLC6A4) Promoter Methylation and Amygdala Response During Negative Emotion Processing in Individuals With Alcohol Dependence.

Similar Datasets

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