Journal
ASIA-PACIFIC PSYCHIATRY
Volume 5, Issue 1, Pages 39-50Publisher
WILEY
DOI: 10.1111/appy.12010
Keywords
alcohol dependence; discordant sib pairs; DNA methylation; epigenetic modification; genome-wide
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Funding
- National Natural Science Foundation of China [20111483, 81171261]
- National Key Basic Research and Development Program (973) [2009CB522007]
- Natural Science Foundation of China [81130020, 81100996, 30900486]
- Henan Science Technology Committee [094200510005]
- Fund for Talents with Innovation in Medical Science and Technology of Henan Province [3052]
- Central Colleges basic scientific research operating expenses [2011QNZT170]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110162120013]
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Introduction Alcohol dependence is a complex disease caused by a confluence of environmental and genetic factors. Epigenetic mechanisms have been shown to play an important role in the pathogenesis of alcohol dependence. Methods To determine if alterations in gene-specific methylation were associated with alcohol dependence, a genome-wide DNA methylation analysis was performed on peripheral blood mononuclear cells from alcohol-dependent patients and siblings without alcohol dependence as controls. The Illumina Infinium Human Methylation450 BeadChip was used and gene-specific methylation of DNA isolated from peripheral blood mononuclear cells was assessed. Genes ALDH1L2, GAD1, DBH and GABRP were selected to validate beadchip results by pyrosequencing. Results Compared to normal controls, 865 hypomethylated and 716 hypermethylated CG sites in peripheral blood mononuclear cell DNA in alcohol-dependent patients were identified. The most hypomethylated CG site is located in the promoter of SSTR4 (somatostatin receptor 4) and the most hypermethylated CG site is GABRP (gamma-aminobutyric acid A receptor). The results from beadchip analysis were consistent with that of pyrosequencing. Discussion DNA methylation might be associated with alcohol dependence. Genes SSTR4, ALDH1L2, GAD1, DBH and GABRP may participate in the biological process of alcohol dependence.
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