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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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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. |
format | Online Article Text |
id | pubmed-5033010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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