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Contact: Jörgen Engel, Ph.D., M.D.
jorgen.engel@pharm.gu.se
46-31-786-3416
University of Gothenburg

Rainer Spanagel, Ph.D.
rainer.spanagel@zi-mannheim.de
49-621-1703-6251
Central Institute of Mental Health

Alcoholism: Clinical & Experimental Research

Peptide ghrelin may be involved in both alcohol dependence and overeating

Ghrelin is a peptide, mainly produced in the stomach, but also found in small amounts in the brain. It is known to affect food intake by increasing feelings of hunger and the urge to eat. A new study has examined ghrelin's role in addictive behaviors. Findings indicate that variations in the genes producing ghrelin and its receptor are more common in individuals considered heavy drinkers.

Results will be published in the December issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Previous research had shown that ghrelin levels in blood plasma are altered in addictive behaviours such as alcohol dependence and compulsive overeating," said Jörgen Engel, professor of pharmacology at the Sahlgrenska Academy, University of Gothenburg.

"It may be that common mechanisms in the brain underlie different forms of addictive behaviours, including compulsive overeating, pathological gambling and drug dependence," he said. "We hypothesized that the ghrelin system may be an important player in the brain-reward systems and, more specifically, wanted to investigate if the ghrelin system is involved in alcohol dependence in humans." Engel is also corresponding author for the study.

Rainer Spanagel, director and chair of psychopharmacology at the Central Institute of Mental Health in Germany, called this study very important for uncovering similar neurobiological mechanisms that seem to underlie overeating and compulsive drug use. "Ghrelin appears to interact with the mesolimbic dopaminergic reward system, which means it may be able to affect the action of drugs of abuse, including alcohol," he said.

For this research, scientists recruited 417 Spanish individuals from the general population (n=279) as well as heavy drinkers (n=138) admitted to a hospital for treatment. The study sample – comprised of abstainers, moderate and heavy alcohol drinkers – was then examined for single nucleotide polymorphisms (SNPs) in the pro-ghrelin and growth hormone secretagogue receptors (GHS-R1A) gene.

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

"Not only are these specific variations in the genes producing ghrelin and its receptor more common in heavy alcohol-using individuals," said Engel, "these variations also seem to have an influence on the body weight of these heavy drinking individuals, as we found an association with an increased body weight in these patients. In other words, if you are a carrier of these genetic variants in the ghrelin or ghrelin receptor gene, you are more susceptible to having multiple addictive behaviours such as alcohol dependence and overeating."

"This is one further important piece of evidence in humans that there is a link between the activity of the ghrelin hormone and the action of alcohol," noted Spanagel.

"Our findings may help to explain the comorbidity of different addictive behaviours such as alcohol addiction and compulsive overeating," said Engel, "providing clues to the genetic basis for the development of these kind of disorders. Ghrelin and its receptor could thus be targets for the development of new drugs for alcohol dependence or a subtype of alcohol-dependent individuals with eating disorders such as compulsive overeating."

###

Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Association of Pro-Ghrelin and GHS-R1A Gene Polymorphisms and Haplotypes with Heavy Alcohol-Use and Body Mass," were: Sara Landgren and Elisabet Jerlhag of the Institute of Neuroscience and Physiology in the Department of Pharmacology at Göteborg University; Henrik Zetterberg and Kaj Blennow of the Institute of Neuroscience and Physiology in the Department of Psychiatry and Neurochemistry at Göteborg University; Arturo Gonzalez-Quintela and Joaquin Campos of the Department of Internal Medicine at the Hospital Clinico Universitario of Santiago de Compostela, Spain; Ulrica Olofsson of the Regional Oncologic Centre of the West Sweden Health Care Region; and Staffan Nilsson of the Department of Mathematical Statistics at Chalmers University of Technology, Sweden. The study was funded by the Swedish Research Council, the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, the Swedish Labour Market Insurance, the Wilhelm and Martina Lungrens Scientific Foundation, the Swedish Council for Tobacco Research, the Signe and Olof Wallenius Foundation, the Goljes memory Foundation, the Sahlgrenska University Hospital, and the Galician Council.



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