A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence

Salim Mottagui-Tabar, Jonathan A. Prince, Claes Wahlestedt, Guanshan Zhu, David Goldman, Markus Heilig

Research output: Contribution to journalArticle

54 Scopus citations

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 (r 2 = 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.

Original languageEnglish (US)
Pages (from-to)702-707
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume29
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Alcohol Dependence
  • Genetic Association Studies
  • Neuropeptide Y Polymorphisms
  • Promoter

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

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