Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
Sci Rep. 2017 Feb 6;7:41816. doi: 10.1038/srep41816.
Altered DNA methylation in addiction-related genes may modify the susceptibility to alcohol or drug dependence (AD or ND). We profiled peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 addiction-related genes in 256 African Americans (AAs) (117 cases with AD-ND codependence and 139 controls) and 196 European Americans (103 cases with AD-ND codependence and 93 controls) using Illumina's GoldenGate DNA methylation array assays. AD-ND codependence-associated DNA methylation changes were analyzed using linear mixed-effects models with consideration of batch effects and covariates age, sex, and ancestry proportions. Seventy CpGs (in 41 genes) showed nominally significant associations (P < 0.05) with AD-ND codependence in both AAs and EAs. One CpG (HTR2B cg27531267) was hypomethylated in AA cases (P = 7.2 × 10), while 17 CpGs in 16 genes (including HTR2B cg27531267) were hypermethylated in EA cases (5.6 × 10 ≤ P ≤ 9.5 × 10). Nevertheless, 13 single nucleotide polymorphisms (SNPs) nearby HTR2B cg27531267 and the interaction of these SNPs and cg27531267 did not show significant effects on AD-ND codependence in either AAs or EAs. Our study demonstrated that DNA methylation changes in addiction-related genes could be potential biomarkers for AD-ND co-dependence. Future studies need to explore whether DNA methylation alterations influence the risk of AD-ND codependence or the other way around.
与成瘾相关的基因中 DNA 甲基化的改变可能会改变对酒精或药物依赖（AD 或 ND）的易感性。我们使用 Illumina 的 GoldenGate DNA 甲基化阵列检测分析了 256 名非裔美国人（AA）（117 例 AD-ND 共病和 139 例对照）和 196 名欧洲裔美国人（103 例 AD-ND 共病和 93 例对照）的 82 个与成瘾相关基因启动子区域中 384 个 CpG 的外周血 DNA 甲基化水平。使用考虑批次效应和协变量年龄、性别和祖先比例的线性混合效应模型分析 AD-ND 共病相关的 DNA 甲基化变化。在 AA 和 EA 中，有 70 个 CpG（41 个基因）与 AD-ND 共病具有名义上的显著关联（P < 0.05）。AA 病例中 1 个 CpG（HTR2B cg27531267）呈低甲基化（P = 7.2 × 10），而 EA 病例中有 17 个 CpG（包括 HTR2B cg27531267）呈高甲基化（5.6 × 10≤P≤9.5 × 10）。然而，HTR2B cg27531267 附近的 13 个单核苷酸多态性（SNP）以及这些 SNP 和 cg27531267 的相互作用在 AA 或 EA 中均未显示对 AD-ND 共病有显著影响。我们的研究表明，与成瘾相关的基因中的 DNA 甲基化变化可能是 AD-ND 共病的潜在生物标志物。未来的研究需要探讨 DNA 甲基化改变是否影响 AD-ND 共病的风险，或者是否存在相反的情况。
