Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes

作者：Xu, Hongqin; Wang, Fan; Kranzler, Henry R.; Gelernter, Joel; Zhang, Huiping^*

来源：Scientific Reports, 2017, 7(1): 41816.

DOI：10.1038/srep41816

• GENOME-WIDE ASSOCIATION
• NATIONAL EPIDEMIOLOGIC SURVEY
• MESSENGER-RNA EXPRESSION
• CIGARETTE-SMOKING BEHAVIORS
• EUROPEAN-AMERICANS
• SUBSTANCE DEPENDENCE
• CHROMATIN-STRUCTURE
• MOLECULAR-GENETICS
• DRUG-DEPENDENCE
• UNITED-STATES

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 x 10(-5)), while 17 CpGs in 16 genes (including HTR2B cg27531267) were hypermethylated in EA cases (5.6 x 10(-9) <= P <= 9.5 x 10(-5)). 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.

• 出版日期2017-2-6
• 单位吉林大学