The 1258 G>A polymorphism in the neuropeptide Y gene is associated with greater alcohol consumption in a Mediterranean population.

Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. In the Spanish Mediterranean population, this variant is not polymorphic. Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruited. Alcohol consumption, and demographic and lifestyle variables were measured. Nucleotide sequence determination and SNP analyses were carried out. Only one exonic SNP was detected by direct sequencing (1258 G>A or rs9785023; allele frequency 0.47). From the intronic markers chosen (483 A>G or rs13235938, 2517 A>G or rs4722342, and 7065 A>G or rs4722343), only the two latter ones were polymorphic (allele frequencies 0.46 and 0.04, respectively), and none of them were associated with alcohol consumption. However, the 1258 G>A SNP was associated (recessive pattern) with higher alcohol intake. This association was particularly relevant in men with high alcohol intake (59.1±5.0 g/day in AA as opposed to 40.6±7.5 in the G carriers, P=.022) and women with moderate alcohol intake (7.3±5.5 g/day in AA as opposed to 4.6±3.9g/day in G carriers, P=.048). The 1258 G>A polymorphism in the NPY is associated with higher alcohol consumption in the Mediterranean population.