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

Autores da FMUP

• Ivone Luísa De Castro Vale

  Autor

• Milton Severo Barros Da Silva

  Autor

• Davide Maurício Costa Carvalho

  Autor

Participantes de fora da FMUP

• Duraes, C
• van Rossum, EFC
• Staufenbiel, SM
• Lemos, MC

Unidades de investigação

• Medicina

• Neurociências Clínicas e Saúde Mental

Abstract

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 9 beta SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans' offspring. The 9 beta variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9 beta variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9 beta risk allele and lifetime PTSD. Carriers of the 9 beta risk allele had significantly lower HCC than non-carriers. We found the 9 beta risk allele and a haplotype comprising the 9 beta risk allele of the GR gene to be associated with PTSD in veterans. This 9 beta risk allele was also associated with lower HCC in their offspring.

Keywords

• posttraumatic stress disorder; genetics; glucocorticoid receptor; single nucleotide polymorphism; war veterans; hair cortisol