{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:53:04Z","timestamp":1777467184383,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associa\u00e7\u00e3o dos Amigos do Servi\u00e7o de Endocrinologia do Hospital de S\u00e3o Jo\u00e3o","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Healthcare"],"abstract":"<jats:p>Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30\u201346% 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 9\u03b2 SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans\u2019 offspring. The 9\u03b2 variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9\u03b2 variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9\u03b2 risk allele and lifetime PTSD. Carriers of the 9\u03b2 risk allele had significantly lower HCC than non-carriers. We found the 9\u03b2 risk allele and a haplotype comprising the 9\u03b2 risk allele of the GR gene to be associated with PTSD in veterans. This 9\u03b2 risk allele was also associated with lower HCC in their offspring.<\/jats:p>","DOI":"10.3390\/healthcare9020173","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Glucocorticoid Receptor Gene (NR3C1) 9\u03b2 SNP Is Associated with Posttraumatic Stress Disorder"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5343-0229","authenticated-orcid":false,"given":"Ivone","family":"Castro-Vale","sequence":"first","affiliation":[{"name":"Medical Psychology Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (Institute for Research and Innovation in Health), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-0708","authenticated-orcid":false,"given":"Cec\u00edlia","family":"Dur\u00e3es","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (Institute for Research and Innovation in Health), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Elisabeth F. C.","family":"van Rossum","sequence":"additional","affiliation":[{"name":"Erasmus MC, Division of Endocrinology, Department of Internal Medicine, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands"}]},{"given":"Sabine M.","family":"Staufenbiel","sequence":"additional","affiliation":[{"name":"Erasmus MC, Division of Endocrinology, Department of Internal Medicine, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands"}]},{"given":"Milton","family":"Severo","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Medical Education and Simulation, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9326-8900","authenticated-orcid":false,"given":"Manuel C.","family":"Lemos","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-3741","authenticated-orcid":false,"given":"Davide","family":"Carvalho","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (Institute for Research and Innovation in Health), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. Jo\u00e3o, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ecl.2013.05.004","article-title":"Endocrine Aspects of Post-traumatic Stress Disorder and Implications for Diagnosis and Treatment","volume":"42","author":"Daskalakis","year":"2013","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jpsychires.2005.08.002","article-title":"Assessment of HPA-axis function in posttraumatic stress disorder: Pharmacological and non-pharmacological challenge tests, a review","volume":"40","author":"Vermetten","year":"2006","journal-title":"J. Psychiatr. 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