Association Between Promoter Methylation of Serotonin Transporter Gene and Depressive Symptoms

A Monozygotic Twin Study

Bibliographic Data

ID19301298
AuthorsJinying Zhao (0000-0003-3243-2660, Tulane University, corresponding author), Jack Goldberg (0000-0003-1979-2530), J Douglas Bremner (0000-0003-1633-6433), Viola Vaccarino (0000-0002-9054-0654)
Year2013
Volume75
Issue6
Pages523-529
Publication date2013-07-01
Peer ReviewedYes
Open AccessNo
TypeARTICLE
VenuePsychosomatic Medicine (JOURNAL)
Journal identifiersISSN: 0033-3174 • E-ISSN: 1534-7796
PublisherOvid Technologies (Wolters Kluwer Health) (PUBLISHER)
DOI10.1097/psy.0b013e3182924cf4
PMID23766378
PMCIDPMC3848698
OpenAlexW2072289007
LanguageEN
Citations received6
References cited49

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

Anxiety · Beck Depression Inventory · Biology · CpG site · DNA methylation · Epigenetics · Gene · Gene expression · Genotype · Heritability · Methylation · Monozygotic twin · Promoter · Psychiatry · Serotonin transporter · Twin study · Epigenetics and DNA Methylation · Genetic Associations and Epidemiology · Genetics · Internal Medicine · Medicine · Tryptophan and brain disorders

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