Genetic variation of the ghrelin signaling system in females with severe alcohol dependence.
BACKGROUND
Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212).


METHODS
Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals.


RESULTS
We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group.


CONCLUSIONS
Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.
Landgren
Sara
S
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. sara.landgren@pharm.gu.se
Jerlhag
Elisabet
E
Hallman
Jarmila
J
Oreland
Lars
L
Lissner
Lauren
L
Strandhagen
Elisabeth
E
Thelle
Dag S
DS
Zetterberg
Henrik
H
Blennow
Kaj
K
Engel
Jörgen A
JA
D000437:Alcoholism / Q000235:genetics*; D015992:Body Mass Index; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D054439:Ghrelin / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054440:Receptors, Ghrelin / Q000235:genetics*; D012907:Smoking / Q000235:genetics
C515349:GHRL protein, human; D054439:Ghrelin; D054440:Receptors, Ghrelin