title: Sex dependent influence of a functional polymorphism in steroid 5-α-reductase type 2 (SRD5A2) on post-traumatic stress symptoms.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gillespie
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Atlanta VA Medical Center, Atlanta, Georgia.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Howard Hughes Medical Institute, Atlanta, Georgia.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kerley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Crain
authors.affiliation: Howard Hughes Medical Institute, Atlanta, Georgia.
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Mercer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Weiss
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Justine
authors.initials: J
authors.lastname: Phifer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Yilang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Max Planck Institute of Psychiatry, Atlanta, Georgia.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Howard Hughes Medical Institute, Atlanta, Georgia.|Yerkes National Primate Research Center, Atlanta, Georgia.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000502:physiology*; D000328:Adult; D001741:Black or African American; D003863:Depression / Q000175:diagnosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013313:Stress Disorders, Post-Traumatic / Q000208:ethnology / Q000235:genetics*; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000378:metabolism; D014947:Wounds and Injuries
chemical_list: D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476567:steroid-5alpha-reductase type 2; D006854:Hydrocortisone