An abundant proneurotensin polymorphism, 479A>G, and a test of its association with alcohol dependence in a Finnish population.
BACKGROUND
Neurotensin is a 13-amino acid neuropeptide that endogenously modulates dopamine release in the central nervous system. In substance dependence, the mesolimbic dopamine system has been postulated to be a central structure that mediates rewarding and reinforcing effects. Neurotensin receptors in the neurons of the ventral tegmental area facilitate dopamine release, making the neurotensin gene an excellent candidate gene for alcohol dependence and for other behaviors that involve reinforcement.


METHODS
A total of 639 psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G polymorphism. We used the polymorphism as a marker to study the association between proneurotensin gene and alcohol dependence by comparing 229 unrelated Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria) subjects who were also criminal offenders. In addition, 276 relatives of the alcohol-dependent and control subjects were genotyped.


RESULTS
The frequencies of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for 479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and 0.06 in controls and alcohol-dependent subjects, respectively, and this difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61, controls vs. alcohol-dependent subjects).


CONCLUSIONS
The results of the comparison between psychiatrically interviewed controls and alcoholics from a relatively well defined population indicate that the proneurotensin 479A>G polymorphism is not strongly associated with alcohol dependence. The results do not rule out a role for this gene in the pathogenesis of alcoholism or in differential vulnerability.
Vanakoski
J
J
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20852, USA. jyrkiv@mail.nih.gov
Mazzanti
C
C
Naukkarinen
H
H
Virkkunen
M
M
Goldman
D
D
D000437:Alcoholism / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D009496:Neurotensin / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*
D011498:Protein Precursors; C411471:proneurotensin; D009496:Neurotensin