title: A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence.
abstract: BACKGROUND
  Neuropeptide Y (NPY) is a major endogenous regulator of anxiety-related behaviors and emotionality. Transgenic work with NPY and null-mutant mice have implicated NPY in the control of alcohol consumption, suggesting that genetic variation of the prepro-NPY gene may also contribute to the heritability of alcoholism. The aim of this study was to examine whether polymorphic variants of the NPY gene are associated with the diagnosis of alcohol dependence.
  
  
  METHODS
  We compared allele frequencies of 5 NPY polymorphisms (-883-ins/del, -602, -399, -84, and +1128) in a Nordic population of alcohol-dependent individuals (n = 428 males; n = 149 females) and ethnically matched controls (n = 84 males; n = 93 females) for whom alcohol dependence or any diagnosis of substance disorder was excluded. Patients were further subtyped into type I (late-onset) and type II (early-onset) alcoholics.
  
  
  RESULTS
  The -602 marker showed a significant association with alcohol dependence (p = 0.0035; OR, 2.3; 95% CI, 1.3-4.0); a trend level association was further observed for the -399 marker (p = 0.058; OR, 1.3; 95% CI, 0.99-1.7) and the +1128 marker (p = 0.053; OR, 1.8; 95% CI, 0.99-3.1). The association for the -602 marker remained and was strengthened when analyzed in type I subjects only, although this association was not seen in type II patients, and there also was a significant association in the female subjects but not in males. The -602 single nucleotide polymorphism was in strong linkage dysequilibrium (r2 = 0.7; p < 0.0001) with the +1128 single nucleotide polymorphism, which has previously been reported to be associated with a diagnosis of alcoholism. Haplotype-based association confirmed these results.
  
  
  CONCLUSIONS
  We report a novel polymorphism at position -602 in the 5' region of the NPY gene that is significantly associated with alcohol dependence. We also describe the haplotype frequencies and linkage dysequilibrium pattern of four variations in that region.
authors.affiliation: Karolinska Institute, Center for Genomics and Bioinformatics, Stockholm, Sweden.
authors.forename: Salim
authors.initials: S
authors.lastname: Mottagui-Tabar
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Prince
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D013548:Sweden
chemical_list: D017931:DNA Primers; D009478:Neuropeptide Y