Association of Pro-Ghrelin and GHS-R1A Gene Polymorphisms and Haplotypes With Heavy Alcohol Use and Body Mass

Authors

  • Sara Landgren,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Elisabet Jerlhag,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Henrik Zetterberg,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Arturo Gonzalez-Quintela,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Joaquin Campos,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Ulrica Olofsson,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Staffan Nilsson,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Kaj Blennow,

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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  • Jörgen A. Engel

    1. From the Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University (SL, EJ, JAE), Göteborg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Göteborg University (HZ, KB), Göteborg, Sweden; Department of Internal Medicine, Hospital Clinico Universitario (AG-Q, JC), Santiago de Compostela, Spain; Regional Oncologic Centre, West Sweden Health Care Region (UO), Göteborg, Sweden; and Department of Mathematical Statistics, Chalmers University of Technology (SN), Göteborg, Sweden.
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Reprint requests: Jörgen A. Engel, Medicinaregatan 13A, POB 431, 405 30 Göteborg, Sweden; Fax: +46 31 786 32 84; E-mail: jorgen.engel@pharm.gu.se

Abstract

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.

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