Association of galanin haplotypes with alcoholism and anxiety in two ethnically distinct populations

Department of Psychiatry, University of Helsinki, Helsinki, Uusimaa, Finland
Molecular Psychiatry (Impact Factor: 14.5). 03/2006; 11(3):301-11. DOI: 10.1038/
Source: PubMed


The neuropeptide galanin (GAL) is widely expressed in the central nervous system. Animal studies have implicated GAL in alcohol abuse and anxiety: chronic ethanol intake increases hypothalamic GAL mRNA; high levels of stress increase GAL release in the central amygdala. The coding sequence of the galanin gene, GAL, is highly conserved and a functional polymorphism has not yet been found. The aim of our study was, for the first time, to identify GAL haplotypes and investigate associations with alcoholism and anxiety. Seven single-nucleotide polymorphisms (SNPs) spanning GAL were genotyped in 65 controls from five populations: US and Finnish Caucasians, African Americans, Plains and Southwestern Indians. A single haplotype block with little evidence of historical recombination was observed for each population. Four tag SNPs were then genotyped in DSM-III-R lifetime alcoholics and nonalcoholics from two population isolates: 514 Finnish Caucasian men and 331 Plains Indian men and women. Tridimensional Personality Questionnaire harm avoidance (HA) scores, a dimensional measure of anxiety, were obtained. There was a haplotype association with alcoholism in both the Finnish (P=0.001) and Plains Indian (P=0.004) men. The SNPs were also significantly associated. Alcoholics were divided into high and low HA groups (>or= and <mean HA of population). In the Finns, haplotype (P<0.0001) and diplotype (P<0.0001) distributions differed between high HA alcoholics, low HA alcoholics and nonalcoholics. Our results from two independent populations suggest that GAL may contribute to vulnerability to alcoholism, perhaps mediated by dimensional anxiety.

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    • "In Finnish and American Plains Indian men , an association of GAL haplotypes with alcoholism has been reported ( Belfer et al . , 2006 ) . Furthermore , the GAL 3 gene , but not the GAL 1 and GAL 2 genes , was associated with alcoholism in Finnish Caucasians ( Belfer et al . , 2007 ) , whereas in the same study , no association of the GAL 3 locus with alcoholism was observed in American Plains Indians . This difference"
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    ABSTRACT: Galanin was first identified 30 years ago as a "classic neuropeptide," with actions primarily as a modulator of neurotransmission in the brain and peripheral nervous system. Other structurally-related peptides-galanin-like peptide and alarin-with diverse biologic actions in brain and other tissues have since been identified, although, unlike galanin, their cognate receptors are currently unknown. Over the last two decades, in addition to many neuronal actions, a number of nonneuronal actions of galanin and other galanin family peptides have been described. These include actions associated with neural stem cells, nonneuronal cells in the brain such as glia, endocrine functions, effects on metabolism, energy homeostasis, and paracrine effects in bone. Substantial new data also indicate an emerging role for galanin in innate immunity, inflammation, and cancer. Galanin has been shown to regulate its numerous physiologic and pathophysiological processes through interactions with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and signaling via multiple transduction pathways, including inhibition of cAMP/PKA (GAL1, GAL3) and stimulation of phospholipase C (GAL2). In this review, we emphasize the importance of novel galanin receptor-specific agonists and antagonists. Also, other approaches, including new transgenic mouse lines (such as a recently characterized GAL3 knockout mouse) represent, in combination with viral-based techniques, critical tools required to better evaluate galanin system physiology. These in turn will help identify potential targets of the galanin/galanin-receptor systems in a diverse range of human diseases, including pain, mood disorders, epilepsy, neurodegenerative conditions, diabetes, and cancer. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
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    • "These include metabolism , feeding and endocrinology, cognition, epilepsy, chronic anxiety and depression, addiction, neuroprotection, neuronal regeneration, and pain (see recent reviews (Lang et al., 2007; Ogren et al., 2010; Picciotto et al., 2010)). Some, but by no means all, of these rodent findings are paralleled by human studies demonstrating associations between single nucleotide polymorphisms (SNPs) in the GAL gene and/or one of its three receptors, and depression or anxiety disorders (Unschuld et al., 2008; Wray et al., 2010; Juhasz et al., 2014) and addictive behaviours that include smoking (Gold et al., 2012), alcohol (Belfer et al., 2006), and heroin (Levran et al., 2008). To date, there are no studies that link the galaninergic system to dietary fat intake or weight regulation in humans, though a single study has shown a relationship with elevated triglyceride levels in familial combined hyperlipidaemia (Plaisier et al., 2009). "
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    • "In addition to these neurotransmitters, there are a number of orexigenic peptides, which in rodents are found to stimulate the consumption of ethanol and to be strongly affected by ethanol [18] [19] [20] [21] and in humans are believed to have a role in alcoholism [22] [23]. These include galanin (GAL) and orexin/hypocretin (OX), which shows increased expression in rats administered or trained to drink ethanol [19] [20] [24] and higher expression in inbred and outbred rodent strains that spontaneously overconsume ethanol [25] [26]. "
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