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Array‐Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence
Author(s) -
Zhang Huiping,
Herman Aryeh I.,
Kranzler Henry R.,
Anton Raymond F.,
Zhao Hongyu,
Zheng Wei,
Gelernter Joel
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01928.x
Subject(s) - methylation , dna methylation , epigenetics , cpg site , biology , promoter , genetics , microbiology and biotechnology , gene , gene expression
Background Epigenetic regulation through DNA methylation may influence vulnerability to numerous disorders, including alcohol dependence ( AD ). Methods Peripheral blood DNA methylation levels of 384 C p G s in the promoter regions of 82 candidate genes were examined in 285 A frican A mericans ( AA s; 141 AD cases and 144 controls) and 249 E uropean A mericans ( EA s; 144 AD cases and 105 controls) using I llumina G olden G ate M ethylation A rray assays. Association of AD and DNA methylation changes was analyzed using multivariate analyses of covariance with frequency of intoxication, sex, age, and ancestry proportion as covariates. C p G s showing significant methylation alterations in AD cases were further examined in a replication sample (49 EA cases and 32 EA controls) using S equenom's M ass ARRAY E pi TYPER technology. Results In AA s, 2 C p G s in 2 genes ( GABRB3 and POMC ) were hypermethylated in AD cases compared with controls ( p ≤ 0.001). In EA s, 6 C p G s in 6 genes ( HTR3A , NCAM1 , DRD4 , MBD3 , HTR2B , and GRIN1 ) were hypermethylated in AD cases compared with controls ( p ≤ 0.001); C p G cg08989585 in the HTR3A promoter region showed a significantly higher methylation level in EA cases than in EA controls after B onferroni correction ( p = 0.00007). Additionally, methylation levels of 6 C p G s (including cg08989585) in the HTR3A promoter region were analyzed in the replication sample. Although the 6 HTR3A promoter C p G s did not show significant methylation differences between EA cases and EA controls ( p = 0.067 to 0.877), the methylation level of C p G cg08989585 was nonsignificantly higher in EA cases (26.9%) than in EA controls (18.6%; p = 0.139). Conclusions The findings from this study suggest that DNA methylation profile appears to be associated with AD in a population‐specific way and the predisposition to AD may result from a complex interplay of genetic variation and epigenetic modifications.