Polymorphism of the neuropeptide Y gene: an association study with alcohol withdrawal

Neuropeptide Y (NPY) exists in both the central and peripheral nervous system and is thought to modulate many functions such as feeding behavior, anxiety-associated behavior, circadian rhythm, seizure modulation, and hormone secretion. Recent studies have revealed that NPY influences alcohol consumption in mice and that alcohol-preferring rats showed lower concentrations of NPY-like immunoreactivity compared with alcohol-nonpreferring rats in several brain regions.

In the present study, we analyzed the whole coding region and 5'-untranslating region of the NPY gene for 163 Japanese male alcoholics with different withdrawal symptoms (93 with delirium tremens, 71 with seizures, 49 with hallucinations) and 98 Japanese male controls. ALDH2 genotypes of all subjects tested were ALDH2*1 homozygote.

Three polymorphic nucleotide substitutions, namely -121C/A (promoter), 1258G/A (exon 2), and 5671C/T (exon 3), were detected in both groups. Substituting C to A in the -121 locus produced a putative binding site of GATA-1 and GATA-2. Also, -90G/A (promoter) as a rare variant and 5642-5651 single nucleotide repeats T10/T11 (intron 2) were found. Polymorphism (C/T) at the 1128 locus has been reported to be associated with a higher serum cholesterol level in obese white subjects, but such a polymorphism was not found in our samples. The genotypical distributions for these polymorphic loci (-121C/A, 1258G/A, 5642-5651 T10/T11, and 5671C/T) were not significantly different between the alcoholics and controls. However, frequency of the T allele and frequency of the genotype that possessed T alleles (CT, TT) at the 5671 locus were significantly higher in patients with seizure than in those without seizure (p < 0.05, p < 0.02).

Our data suggested that a C to T substitution at the 5671 locus of the NPY gene may be associated with seizure during alcohol withdrawal.