Alcoholism is associated with GALR3 but not two other galanin receptor genes

• Published in: Genes, brain and behavior Vol. 6; no. 5; pp. 473 - 481
• Main Authors: Belfer, I., Hipp, H., Bollettino, A., McKnight, C., Evans, C., Virkkunen, M., Albaugh, B., Max, M. B., Goldman, D., Enoch, M. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-2007
• Subjects: Adult; Alcoholism; Alcoholism - genetics; Analysis of Variance; association study; Case-Control Studies; Finland; galanin; galanin receptor; Genetic Predisposition to Disease - genetics; haplotype; Haplotypes; Humans; Linkage Disequilibrium; Male; Odds Ratio; Polymorphism, Single Nucleotide; Receptor, Galanin, Type 1 - genetics; Receptor, Galanin, Type 2 - genetics; Receptor, Galanin, Type 3 - genetics; Reference Values; Risk Factors; single‐nucleotide polymorphism; Finland
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/j.1601-183X.2006.00275.x

The neuropeptide galanin is widely expressed in the periphery and the central nervous system and mediates diverse physiological processes and behaviors including alcohol abuse, depression and anxiety. Four genes encoding galanin and its receptors have been identified (GAL, GALR1, GALR2 and GALR3). Recently we found that GAL haplotypes were associated with alcoholism, raising the possibility that genetic variation in GALR1, GALR2 and GALR3 might also alter alcoholism risk. Tag single nucleotide polymorphisms (SNPs) were identified by genotyping SNP panels in controls from five populations. For the association study with alcoholism, six GALR1, four GALR2 and four GALR3 SNPs were genotyped in a large cohort of Finnish alcoholics and non‐alcoholics. GALR3 showed a significant association with alcoholism that was driven by one SNP (rs3091367). Moreover, the combination of the GALR3 rs3091367 risk allele and GAL risk haplotypes led to a modestly increased odds ratio (OR) for alcoholism (2.4) as compared with the effect of either GAL (1.9) or GALR3 alone (1.4). Likewise, the combination of the GALR3 and GAL risk diplotypes led to an increased OR for alcoholism (4.6) as compared with the effect of either GAL (2.0) or GALR3 alone (1.6). There was no effect of GALR1 or GALR2 on alcoholism risk. This evidence suggests that GALR3 mediates the alcoholism‐related actions of galanin.