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The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30–46% of the variance in PTSD, no associations have been found between single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene (NR3C1) and risk for th...

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Autores principales: Castro-Vale, Ivone, Durães, Cecília, van Rossum, Elisabeth F. C., Staufenbiel, Sabine M., Severo, Milton, Lemos, Manuel C., Carvalho, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915937/
https://www.ncbi.nlm.nih.gov/pubmed/33562675
http://dx.doi.org/10.3390/healthcare9020173
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author Castro-Vale, Ivone
Durães, Cecília
van Rossum, Elisabeth F. C.
Staufenbiel, Sabine M.
Severo, Milton
Lemos, Manuel C.
Carvalho, Davide
author_facet Castro-Vale, Ivone
Durães, Cecília
van Rossum, Elisabeth F. C.
Staufenbiel, Sabine M.
Severo, Milton
Lemos, Manuel C.
Carvalho, Davide
author_sort Castro-Vale, Ivone
collection PubMed
description Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30–46% of the variance in PTSD, no associations have been found between single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene (NR3C1) and risk for this disorder. We studied the association of five SNPs in the GR gene (rs10052957, rs6189/rs6190, rs6195, rs41423247, and rs6198) and haplotypes with PTSD, in a group of Portuguese male war veterans (33 with lifetime PTSD, 28 without). To determine whether the 9β SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans’ offspring. The 9β variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9β variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9β risk allele and lifetime PTSD. Carriers of the 9β risk allele had significantly lower HCC than non-carriers. We found the 9β risk allele and a haplotype comprising the 9β risk allele of the GR gene to be associated with PTSD in veterans. This 9β risk allele was also associated with lower HCC in their offspring.
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spelling pubmed-79159372021-03-01 The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder Castro-Vale, Ivone Durães, Cecília van Rossum, Elisabeth F. C. Staufenbiel, Sabine M. Severo, Milton Lemos, Manuel C. Carvalho, Davide Healthcare (Basel) Article Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30–46% of the variance in PTSD, no associations have been found between single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene (NR3C1) and risk for this disorder. We studied the association of five SNPs in the GR gene (rs10052957, rs6189/rs6190, rs6195, rs41423247, and rs6198) and haplotypes with PTSD, in a group of Portuguese male war veterans (33 with lifetime PTSD, 28 without). To determine whether the 9β SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans’ offspring. The 9β variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9β variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9β risk allele and lifetime PTSD. Carriers of the 9β risk allele had significantly lower HCC than non-carriers. We found the 9β risk allele and a haplotype comprising the 9β risk allele of the GR gene to be associated with PTSD in veterans. This 9β risk allele was also associated with lower HCC in their offspring. MDPI 2021-02-05 /pmc/articles/PMC7915937/ /pubmed/33562675 http://dx.doi.org/10.3390/healthcare9020173 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Castro-Vale, Ivone
Durães, Cecília
van Rossum, Elisabeth F. C.
Staufenbiel, Sabine M.
Severo, Milton
Lemos, Manuel C.
Carvalho, Davide
The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title_full The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title_fullStr The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title_full_unstemmed The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title_short The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
title_sort glucocorticoid receptor gene (nr3c1) 9β snp is associated with posttraumatic stress disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915937/
https://www.ncbi.nlm.nih.gov/pubmed/33562675
http://dx.doi.org/10.3390/healthcare9020173
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