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Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
Author(s) -
Suchankova Petra,
Nilsson Staffan,
Pahlen Bettina,
Santtila Pekka,
Sandnabba Kenneth,
Johansson Ada,
Jern Patrick,
Engel Jörgen A.,
Jerlhag Elisabet
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12277
Subject(s) - alcohol use disorders identification test , ghrelin , single nucleotide polymorphism , growth hormone secretagogue receptor , addiction , snp , minor allele frequency , medicine , alcohol use disorder , endocrinology , allele , genetics , psychology , biology , receptor , gene , psychiatry , alcohol , genotype , environmental health , poison control , injury prevention , biochemistry
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 ( SNP s) 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 ( G ln90 L eu) and rs696217 ( L eu72 M et), and one in GHSR , rs2948694, were genotyped in a subset ( n = 4161) of a F innish population‐based cohort, the G enetics of S exuality and A ggression 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.