title: Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking.
abstract: The multifaceted gut-brain peptide ghrelin and its receptor (GHSR-1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre-clinical models, we have shown that ghrelin increases whereas GHSR-1a antagonists decrease alcohol consumption and the motivation to consume alcohol in rodents. Moreover, ghrelin signaling is required for the rewarding properties of addictive drugs including alcohol and nicotine in rodents. Given the hereditary component underlying addictive behaviors and disorders, we sought to investigate whether single nucleotide polymorphisms (SNPs) located in the pre-proghrelin gene (GHRL) and GHSR-1a gene (GHSR) are associated with alcohol use, measured by the alcohol use disorders identification test (AUDIT) and smoking. Two SNPs located in GHRL, rs4684677 (Gln90Leu) and rs696217 (Leu72Met), and one in GHSR, rs2948694, were genotyped in a subset (n = 4161) of a Finnish population-based cohort, the Genetics of Sexuality and Aggression project. The effect of these SNPs on AUDIT scores and smoking was investigated using linear and logistic regressions, respectively. We found that the minor allele of the rs2948694 SNP was nominally associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model). Furthermore, post hoc analyses showed that this risk allele was also associated with increased likelihood of having high level of alcohol problems as determined by AUDIT scores ≥ 16 (P = 0.0043, recessive model). These convergent findings lend further support for the hypothesized involvement of ghrelin signaling in addictive disorders.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Suchankova
authors.affiliation: Department of Mathematical Statistics, Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Bettina
authors.initials: B
authors.lastname: von der Pahlen
authors.affiliation: Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Santtila
authors.affiliation: Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sandnabba
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Ada
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.|Department of Behavioral Sciences and Philosophy, University of Turku, Turku, Finland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jern
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jörgen A
authors.initials: JA
authors.lastname: Engel
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Jerlhag
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000235:genetics*; D005260:Female; D005838:Genotype; D054439:Ghrelin / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054440:Receptors, Ghrelin / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
chemical_list: C515349:GHRL protein, human; D054439:Ghrelin; D054440:Receptors, Ghrelin
keywords: Candidate gene association study; gastrointestinal hormones; substance use disorder