Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with heavy alcohol use and body mass.
BACKGROUND
Ghrelin, an orexigenic peptide, acts on growth hormone secretagogue receptors (GHS-R1A), expressed in the hypothalamus as well as in important reward nodes such as the ventral tegmental area. Interestingly, ghrelin has been found to activate an important part of the reward systems, i.e., the cholinergic-dopaminergic reward link. Additionally, the rewarding and neurochemical properties of alcohol are, at least in part, mediated via this reward link. There is comorbidity between alcohol dependence and eating disorders. Thus, plasma levels of ghrelin are altered in patients with addictive behaviors such as alcohol and nicotine dependence and in binge eating disorder. This overlap prompted as to investigate the pro-ghrelin and GHS-R1A genes in a haplotype analysis of heavy alcohol-using individuals.


METHODS
A total of 417 Spanish individuals (abstainers, moderate, and heavy alcohol drinkers) were investigated in a haplotype analysis of the pro-ghrelin and GHS-R1A genes. Tag SNPs were chosen using HapMap data and the Tagger and Haploview softwares. These SNPs were then genotyped using TaqMan Allelic Discrimination.


RESULTS
SNP rs2232165 of the GHS-R1A gene was associated with heavy alcohol consumption and SNP rs2948694 of the same gene as well as haplotypes of both the pro-ghrelin and the GHS-R1A genes were associated with body mass in heavy alcohol consuming individuals.


CONCLUSIONS
The present findings are the first to disclose an association between the pro-ghrelin and GHS-R1A genes and heavy alcohol use, further strengthening the role of the ghrelin system in addictive behaviors and brain reward.
Landgren
Sara
S
Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University, Göteborg, Sweden.
Jerlhag
Elisabet
E
Zetterberg
Henrik
H
Gonzalez-Quintela
Arturo
A
Campos
Joaquin
J
Olofsson
Ulrica
U
Nilsson
Staffan
S
Blennow
Kaj
K
Engel
Jörgen A
JA
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics*; D000437:Alcoholism / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D015992:Body Mass Index; D005260:Female; D054439:Ghrelin / Q000097:blood / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D054440:Receptors, Ghrelin / Q000097:blood / Q000235:genetics*; D012201:Reward
C515349:GHRL protein, human; D054439:Ghrelin; D054440:Receptors, Ghrelin