This work was supported by grants from the Swedish Medical Research Council and the Söderström-Königska Foundation and the National Institute on Alcohol Abuse and Alcoholism.
A Novel Single Nucleotide Polymorphism of the Neuropeptide Y (NPY) Gene Associated With Alcohol Dependence
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 29, Issue 5, pages 702–707, May 2005
How to Cite
Mottagui-Tabar, S., Prince, J. A., Wahlestedt, C., Zhu, G., Goldman, D. and Heilig, M. (2005), A Novel Single Nucleotide Polymorphism of the Neuropeptide Y (NPY) Gene Associated With Alcohol Dependence. Alcoholism: Clinical and Experimental Research, 29: 702–707. doi: 10.1097/01.ALC.0000164365.04961.B1
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication December 24, 2004; accepted February 20, 2005.
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.
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.
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.
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.