Document Detail


Association between promoter methylation of serotonin transporter gene and depressive symptoms: a monozygotic twin study.
MedLine Citation:
PMID:  23766378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs.
METHODS: DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value).
RESULTS: Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9-7.9, p = .01).
CONCLUSIONS: This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association.
Authors:
Jinying Zhao; Jack Goldberg; James D Bremner; Viola Vaccarino
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Twin Study     Date:  2013-06-13
Journal Detail:
Title:  Psychosomatic medicine     Volume:  75     ISSN:  1534-7796     ISO Abbreviation:  Psychosom Med     Publication Date:    2013 Jul-Aug
Date Detail:
Created Date:  2013-07-04     Completed Date:  2014-03-10     Revised Date:  2014-06-04    
Medline Journal Info:
Nlm Unique ID:  0376505     Medline TA:  Psychosom Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  523-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
CpG Islands
DNA Methylation*
Depression / genetics*,  psychology
Depressive Disorder, Major / genetics,  psychology
Epigenesis, Genetic
Humans
Linear Models
Male
Middle Aged
Promoter Regions, Genetic*
Serotonin Plasma Membrane Transport Proteins / genetics*
Stress Disorders, Post-Traumatic / genetics,  psychology
Twins, Monozygotic / genetics*,  psychology
Veterans / psychology
Grant Support
ID/Acronym/Agency:
K01 AG034259/AG/NIA NIH HHS; K01AG034259/AG/NIA NIH HHS; K24 HL077506/HL/NHLBI NIH HHS; K24 MH076955/MH/NIMH NIH HHS; K24HL077506/HL/NHLBI NIH HHS; R01 AG026255/AG/NIA NIH HHS; R01 DK091369/DK/NIDDK NIH HHS; R01 HL068630/HL/NHLBI NIH HHS; R01 HL088726/HL/NHLBI NIH HHS; R01 MH056120/MH/NIMH NIH HHS; R01AG026255/AG/NIA NIH HHS; R01HL68630/HL/NHLBI NIH HHS; R21 HL092363/HL/NHLBI NIH HHS; R21HL092363/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins
Comments/Corrections
Comment In:
Psychosom Med. 2013 Jul-Aug;75(6):520-2   [PMID:  23788696 ]
Psychosom Med. 2014 Apr;76(3):244-6   [PMID:  24632895 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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