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.
Keywords: NR3C1; genetics; glucocorticoid receptor; hair cortisol; posttraumatic stress disorder; single nucleotide polymorphism; war veterans.