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

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 m...

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Autores principales: Suchankova, Petra, Nilsson, Staffan, von der Pahlen, Bettina, Santtila, Pekka, Sandnabba, Kenneth, Johansson, Ada, Jern, Patrick, Engel, Jörgen A., Jerlhag, Elisabet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033010/
https://www.ncbi.nlm.nih.gov/pubmed/26059200
http://dx.doi.org/10.1111/adb.12277
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author Suchankova, Petra
Nilsson, Staffan
von der Pahlen, Bettina
Santtila, Pekka
Sandnabba, Kenneth
Johansson, Ada
Jern, Patrick
Engel, Jörgen A.
Jerlhag, Elisabet
author_facet Suchankova, Petra
Nilsson, Staffan
von der Pahlen, Bettina
Santtila, Pekka
Sandnabba, Kenneth
Johansson, Ada
Jern, Patrick
Engel, Jörgen A.
Jerlhag, Elisabet
author_sort Suchankova, Petra
collection PubMed
description 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.
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spelling pubmed-50330102016-10-03 Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking Suchankova, Petra Nilsson, Staffan von der Pahlen, Bettina Santtila, Pekka Sandnabba, Kenneth Johansson, Ada Jern, Patrick Engel, Jörgen A. Jerlhag, Elisabet Addict Biol Human Genetic Studies 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. John Wiley and Sons Inc. 2015-06-09 2016-03 /pmc/articles/PMC5033010/ /pubmed/26059200 http://dx.doi.org/10.1111/adb.12277 Text en © 2015 Society for the Study of Addiction This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Human Genetic Studies
Suchankova, Petra
Nilsson, Staffan
von der Pahlen, Bettina
Santtila, Pekka
Sandnabba, Kenneth
Johansson, Ada
Jern, Patrick
Engel, Jörgen A.
Jerlhag, Elisabet
Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title_full Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title_fullStr Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title_full_unstemmed Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title_short Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
title_sort genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking
topic Human Genetic Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033010/
https://www.ncbi.nlm.nih.gov/pubmed/26059200
http://dx.doi.org/10.1111/adb.12277
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