Lastly, although of limited usefulness as a clinical biomarker due to low specificity, six studies assessing global methylation levels were found. The first [103], found striking differences in global methylation, with hypermethylation of +10% as measured in HpaII/MspI digestion fragments and cytosine extension. A later study using the same technique found smaller (+7%) difference of methylation in alcoholics as compared to controls [79]. However follow-up studies by others [31,104] failed to replicate this difference when using a different method, bisulfite pyrosequencing of global LINE-1 elements, although a modest difference (0.2%) in Alu methylation was found by the same methods in one study [104]. It is likely that this difference is due in part to different techniques used. A fifth group [105] found no effect of stratified alcohol intake on global methylation, but did report a weak interaction between alcohol and folate intake on methylation. Postmortem studies in human brain tissue have shown mixed results regarding global methylation, with one showing global hypomethylation as measured by Qpcr [106], but another showing no significant differences [107]. Most recently, Semmler and colleagues also recently reported global hypermethylation in lymphocytes was correlated with alcohol consumption and smoking on treatment entry for alcohol detoxification [108].
