Sex Dependent Influence of a Functional Polymorphism in Steroid 5-α-Reductase Type 2 (SRD5A2) on Post-Traumatic Stress Symptoms

• Type of Material: Article
• Authors: Charles Gillespie, Emory University; Lynn M. Almli, Emory University; Alicia K Smith, Emory University; Bekh Bradley-Davino, Emory University; Kimberly Kerley, Howard Hughes Medical Institute; Daniel F. Crain, Emory University; Kristina B. Mercer, Howard Hughes Medical Institute; Tamara E Weiss, Emory University; Justine Phifer, Emory University; Yilang Tang, Emory University; Joseph F Cubells, Emory University; Elisabeth B. Binder, Emory University; Karen N Conneely, Emory University; Kerry J. Ressler, Emory University
• Language: English
• Date: 2013-04
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.32147/abstract
• Title of Journal or Parent Work: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
• ISSN: 1552-4841
• Volume: 0
• Issue: 3
• Start Page: 283
• End Page: 292
• Grant/Funding Information: Support was also received from National Institute of Mental Health (MH082256 to C.F.G.), Emory and Grady Memorial Hospital General Clinical Research Center, NIH National Centers for Research Resources (M01RR00039 and P20RR16435), NARSAD (C.F.G.), the American Foundation for Suicide Prevention (B.B.) and the Burroughs Wellcome Fund (K.J.R.).; This work was primarily supported by National Institutes of Mental Health (MH071537).
• Keywords: trauma; genetic; cortisol; male; African-American; testosterone; PTSD; human; civilian
• Research Categories: Psychology, General; Biology, Genetics

Abstract

A non-synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5-α-reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post-traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African-American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post-traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex-dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex-specific way, the severity of post-traumatic stress symptoms and risk for diagnosis of PTSD.