Landgren Sara, Jerlhag Elisabet, Zetterberg Henrik, Gonzalez-Quintela Arturo, Campos Joaquin, Olofsson Ulrica, Nilsson Staffan, Blennow Kaj, Engel Jörgen A
Institute of Neuroscience and Physiology, Department of Pharmacology, Göteborg University, Göteborg, Sweden.
Alcohol Clin Exp Res. 2008 Dec;32(12):2054-61. doi: 10.1111/j.1530-0277.2008.00793.x. Epub 2008 Sep 25.
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.
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.
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.
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.
胃饥饿素是一种促食欲肽，作用于生长激素促分泌素受体（GHS-R1A），该受体在下丘脑以及诸如腹侧被盖区等重要奖赏中枢均有表达。有趣的是，胃饥饿素已被发现可激活奖赏系统的一个重要部分，即胆碱能-多巴胺能奖赏通路。此外，酒精的奖赏和神经化学特性至少部分是通过该奖赏通路介导的。酒精依赖与饮食失调之间存在共病现象。因此，在患有酒精和尼古丁依赖等成瘾行为的患者以及暴饮暴食症患者中，胃饥饿素的血浆水平会发生改变。这种重叠促使我们在大量饮酒个体的单倍型分析中研究前胃饥饿素和GHS-R1A基因。
在对前胃饥饿素和GHS-R1A基因进行单倍型分析时，共研究了417名西班牙个体（戒酒者、适度饮酒者和大量饮酒者）。利用HapMap数据以及Tagger和Haploview软件选择标签单核苷酸多态性（SNP）。然后使用TaqMan等位基因鉴别法对这些SNP进行基因分型。
GHS-R1A基因的SNP rs2232165与大量饮酒有关，同一基因的SNP rs2948694以及前胃饥饿素和GHS-R1A基因的单倍型与大量饮酒个体的体重有关。
本研究结果首次揭示了前胃饥饿素和GHS-R1A基因与大量饮酒之间的关联，进一步强化了胃饥饿素系统在成瘾行为和脑奖赏中的作用。
