Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
Journal article, 2016

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.

substance use disorder

Candidate gene association study

gastrointestinal hormones

Author

Petra Suchankova

University of Gothenburg

Staffan Nilsson

Chalmers, Mathematical Sciences, Mathematical Statistics

University of Gothenburg

Bettina von der Pahlen

Åbo Akademi

Pekka Santtila

Åbo Akademi

Kenneth Sandnabba

Åbo Akademi

Ada Johansson

University of Gothenburg

Patrick Jern

Åbo Akademi

University of Turku

Jörgen Engel

University of Gothenburg

Elisabeth Jerlhag

University of Gothenburg

Addiction Biology

1355-6215 (ISSN) 1369-1600 (eISSN)

Vol. 21 2 481-488

Subject Categories

Medical Genetics

DOI

10.1111/adb.12277

PubMed

26059200

More information

Latest update

8/7/2018 1