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DNA methylation patterns in alcoholics and family controls

World Journal of Gastrointestinal Oncology 2012年第6期4卷 138-144页

作者： manish Thapar Jonathan Covault Victor Hesselbrock Herbert L Bonkovsky Department of medicine The University of Connecticut Health Center Farmington CT 06030 United States The Liver-Biliary-Pancreatic Center The University of Connecticut Health Center Farmington CT 06030 United States Department of Psychiatry The University of Connecticut Health Center Farmington CT 06030 United States The Alcohol Research Center The University of Connecticut Health Center Farmington CT 06030 United States The Liver-Biliary-Pancreatic Center Carolinas Medical Center Suite 201 Cannon Research Center 1542 Garden Terrace Charlotte NC 28203 United States

AIm: To assess whether DNA methylation patterns in chronic alcoholics are different from non-alcoholic sibling controls. mETHODS: We examined the methylation patterns in DNA samples from 25 chronic alcoholics and 22 matched siblings as controls (one per family). DNA was extracted from peripheral blood and analyzed for differences in the methylation patterns after bisulfite-conversion. We used the Illumina GoldenGate methylation Cancer Panel I (Illumina, San Diego, CA), which probes the methylation profile at 1505 CpG sites from 807 cancer related genes. We excluded the 84 X-chromosome CpG sites and 134 autosomal CpG sites that failed to show a within sample reliability score of at least 95% for all samples, leaving 1287 autosomal CpG sites (associated with 743 autosomal genes) with reliable signals for all samples. A methylation score was calculated as the average methylation for the 1287 CpG sites examined. Differences were assessed by a two-sample t-test. We also examined the average sib pair differences in methylation scores at each of the 1287 sites. All analyses were performed using SPSS, version 9.0, P methylation levels at the 1287 CpG sites averaged 28.2% for both alcoholics and controls. The mean difference in methylation scores between alcoholic and non-alcoholic sibs by CpG site was mall inter-individual variances; and only 5 CpG sites had an average sib difference > 5%. Subgroup analysis showed that methylation scores were significantly lower for the alcoholic-dependent subjects who smoked compared to their non-smoking unaffected siblings. Specifically, among smokers who are alcoholic, global methylation indices were significantly lower than in non-alcoholic sib controls, whereas among non-smoking alcoholics, the global indices were significantly higher (P = 0.008). CONCLUSION: Although we observed no effect of alcoholism alone on DNA methylation, there is a decrease in alcoholics who smoke, suggesti

关键词： DNA methylation Alcohol Epigenetics Cancer Carcinogenesis Smoking Cigarettes Tobacco

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