Joint analysis of the NACP-REP1 marker within the alpha synuclein gene concludes association with alcohol dependence

Various studies have linked alcohol dependence phenotypes to chromosome 4. One candidate gene is NACP (non-amyloid component of plaques), coding for alpha synuclein. Recently, it has been shown that alpha synuclein mRNA is increased in alcohol-dependent patients within withdrawal state. This increase is significantly associated with craving, especially obsessive craving. On the basis of these observations, the present study analysed two polymorphic repeats within the NACP gene. We found highly significant longer alleles of NACP-REP1 in alcohol-dependent patients compared with healthy controls (Kruskal-Wallis test, x(2) = 99.5; df = 3, P < 0.001). In addition, these lengths significantly correlate with levels of expressed alpha synuclein mRNA (x(2) =8.83; df = 2, P = 0.012). The present results point to a novel approach for a genetic determination of craving, a key factor in the genesis and maintenance not only of alcoholism but also of addiction in general.