M., Haschemi Nassab M., Rhein L., Hagemeier M., Kaeser M., Muschler A., Glahn A., Pich A., Heberlein J., Kornhuber S., Bleich H., Frieling T., Hillemacher Supplementary Material for: Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort. Alcohol dependence;Epigenetics;ALDH2;rs886205 2017-01-13
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Impaired_Regulation_of_ALDH2_Protein_Expression_Revealing_a_Yet_Unknown_Epigenetic_Impact_of_rs886205_on_Specific_Methylation_of_a_Negative_Regulatory_Promoter_Region_in_Alcohol-Dependent_Patients/4547218
10.6084/m9.figshare.4547218.v1