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Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue
INTRODUCTION: The nicotinic α5 receptor subunit, encoded by CHRNA5, harbors multiple functional single nucleotide polymorphisms (SNPs) that affect mRNA expression and alter the encoded protein. These polymorphisms are most notably associated with drug-taking behaviors and cognition. We previously id...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917931/ https://www.ncbi.nlm.nih.gov/pubmed/27350810 http://dx.doi.org/10.1186/s41021-015-0020-x |
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author | Ramsay, Jessica E. Rhodes, C. Harker Thirtamara-Rajamani, Keerthi Smith, Ryan M. |
author_facet | Ramsay, Jessica E. Rhodes, C. Harker Thirtamara-Rajamani, Keerthi Smith, Ryan M. |
author_sort | Ramsay, Jessica E. |
collection | PubMed |
description | INTRODUCTION: The nicotinic α5 receptor subunit, encoded by CHRNA5, harbors multiple functional single nucleotide polymorphisms (SNPs) that affect mRNA expression and alter the encoded protein. These polymorphisms are most notably associated with drug-taking behaviors and cognition. We previously identified common SNPs in a distant regulatory element (DRE) that increase CHRNA5 mRNA expression in the human prefrontal cortex (PFC) and confer risk for nicotine dependence. Genome-wide epigenetic studies in PFC and adipose tissue find strong effects of the DRE SNPs on CpG methylation. However, it is unclear whether DRE SNPs influence CpG methylation en route to modulating CHRNA5 mRNA expression. It is also unclear whether these polymorphisms affect expression in other brain regions, especially those mediating drug-taking behaviors. RESULTS: By measuring total and allelic CHRNA5 mRNA expression in human habenula and putamen autopsy tissues, we found that CHRNA5 DRE variants considerably increase mRNA expression by up to 3.5-fold in both brain regions. Our epigenetic analysis finds no association between CpG methylation and CHRNA5 mRNA expression in the PFC or adipose tissues. CONCLUSIONS: These finding suggests the mechanisms responsible for the genetic modulation of CpG methylation and mRNA expression are independent despite the DRE SNPs being highly associated with both measures. Our findings support a strong association between the DRE SNPs and mRNA expression or CpG methylation in the brain and periphery, but the independence of the two measures leads us to conclude that environmental factors affecting CpG methylation do not appear to directly modulate gene expression. |
format | Online Article Text |
id | pubmed-4917931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49179312016-06-27 Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue Ramsay, Jessica E. Rhodes, C. Harker Thirtamara-Rajamani, Keerthi Smith, Ryan M. Genes Environ Research Article INTRODUCTION: The nicotinic α5 receptor subunit, encoded by CHRNA5, harbors multiple functional single nucleotide polymorphisms (SNPs) that affect mRNA expression and alter the encoded protein. These polymorphisms are most notably associated with drug-taking behaviors and cognition. We previously identified common SNPs in a distant regulatory element (DRE) that increase CHRNA5 mRNA expression in the human prefrontal cortex (PFC) and confer risk for nicotine dependence. Genome-wide epigenetic studies in PFC and adipose tissue find strong effects of the DRE SNPs on CpG methylation. However, it is unclear whether DRE SNPs influence CpG methylation en route to modulating CHRNA5 mRNA expression. It is also unclear whether these polymorphisms affect expression in other brain regions, especially those mediating drug-taking behaviors. RESULTS: By measuring total and allelic CHRNA5 mRNA expression in human habenula and putamen autopsy tissues, we found that CHRNA5 DRE variants considerably increase mRNA expression by up to 3.5-fold in both brain regions. Our epigenetic analysis finds no association between CpG methylation and CHRNA5 mRNA expression in the PFC or adipose tissues. CONCLUSIONS: These finding suggests the mechanisms responsible for the genetic modulation of CpG methylation and mRNA expression are independent despite the DRE SNPs being highly associated with both measures. Our findings support a strong association between the DRE SNPs and mRNA expression or CpG methylation in the brain and periphery, but the independence of the two measures leads us to conclude that environmental factors affecting CpG methylation do not appear to directly modulate gene expression. BioMed Central 2015-10-01 /pmc/articles/PMC4917931/ /pubmed/27350810 http://dx.doi.org/10.1186/s41021-015-0020-x Text en © The Author(s) 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ramsay, Jessica E. Rhodes, C. Harker Thirtamara-Rajamani, Keerthi Smith, Ryan M. Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title | Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title_full | Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title_fullStr | Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title_full_unstemmed | Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title_short | Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue |
title_sort | genetic influences on nicotinic α5 receptor (chrna5) cpg methylation and mrna expression in brain and adipose tissue |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917931/ https://www.ncbi.nlm.nih.gov/pubmed/27350810 http://dx.doi.org/10.1186/s41021-015-0020-x |
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