DNA METHYLATION AND SUBCLINICAL VITAMIN DEFICIENCY OF FOLATE, PYRIDOXAL-PHOSPHATE AND VITAMIN-B12 IN CHRONIC-ALCOHOLICS

Alcohol abuse is known to adversely affect folate, vitamin B12 and pyr idoxal-phosphate metabolism, which are required for de novo synthesis of methionine. Methionine is the precursor of S-adenosylmethionine, th e principal methylating agent in the organism, including DNA. The obje ctive of this study was to measure DNA methylation in peripheral lymph ocytes and the circulating concentrations of these three vitamins in c hronic alcoholics. DNA methylation was assessed by measuring DNA methy l accepting capacity in the presence of Sss1 methylase. Serum pyridoxa l-phosphate and red blood cell folate concentrations were significantl y depressed in alcoholics (P < 0.0001 and P = 0.02, respectively). DNA from patients who consumed 3.0 g/ethanol/kg/day or more, incorporated significantly more (H-3) methyl groups, which reflects a lower state of intrinsic methylation (P = 0.01). DNA hypomethylation was also more pronounced in malnourished alcoholics (P = 0.03). We conclude that he avy ethanol consumption is associated with folate and vitamin B6 deple tion, which may interfere with DNA methylation status by impairing de novo methionine synthesis.