PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Gillespie, Charles F.,2013 PMID: 2014-15550-007
Citation	Gillespie, C. F., et al. (2013). "Sex dependent influence of a functional polymorphism in steroid 5-a-reductase type 2 (SRD5A2) on post-traumatic stress symptoms." American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 162(3): 283-292.
Phenotype	Total PTSD symptoms, Hyperarousal symptoms, Avoidance/Numbing symptoms, Intrusive/Reexperiencing symptoms, Proxy-diagnosis of PTSD
Trauma	Various
Study Design	Case-control
Study Type	Candidate gene association study, Gene-environment interaction study
Sample Size	1,443 subjects
SNP/Marker Size	1 SNP
Predominant Ethnicity	Black
Population	African American
Gender	Sample1(n=780): 61.8% female. Sample2(n=663): 64.1% female.
Age	Sample1: mean age=40.3 years. Sample2: mean age=38.3 years.

Detail Info

Sample Diagnosis	DSM-IV
Related Diagnostic Tools	Childhood trauma questionnaire (CTQ), Traumatic events inventory (TEI), PTSD symptom scale (PSS), Beck depressioninventory (BDI)
Sample Status	This study utilized two different, concurrently obtained, cohorts (Samples 1 and 2) from the Grady Trauma Project (e.g., Binder et al., 2008; Bradley et al., 2008; Gillespie et al., 2009; Ressler et al.,2011).
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	A non-synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5-a-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 x genotype interaction P-value<0.002; males: n=536, P-value<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.
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 5)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs523349	Avoidance/Numbing symptoms	SRD5A2	In males, n=536, T=3.111, P-value=0.0020, permutation P-value=0.0020; in females, P-value>0.3.	In males, we found a significant association with PTSD sympt...... In males, we found a significant association with PTSD symptom severity on all three PSS subscale scores, there were no associations with PSS subscales in females. More...	Significant
rs523349	Intrusive/Reexperiencing symptoms	SRD5A2	In males, n=536, T=2.934, P-value=0.0035, permutation P-value=0.0038; in females, P-value>0.3.	In males, we found a significant association with PTSD sympt...... In males, we found a significant association with PTSD symptom severity on all three PSS subscale scores, there were no associations with PSS subscales in females. More...	Significant
rs523349	Proxy-diagnosis of PTSD	SRD5A2	In male subjects: N=536, P-value=0.013, permutation P-value=0.013; OR=1.456, CI=1.083-1.957. In females: N=907, P-value=0.207; OR=0.8671, CI=0.6949-1.082.	We observed a significant association between SRD5A2 -V89L g...... We observed a significant association between SRD5A2 -V89L genotype and proxy-diagnosis of PTSD in male subjects. Conversely, SRD5A2 -V89L genotype did not predict PTSD proxy-diagnosis in female. More...	Significant
rs523349	Total PTSD symptoms	SRD5A2	C allele and total PTSD symptoms(as measured by PSS), in Sample1: in male subjects: n=298, T=2.169, P-value=0.03, in female subjects: n=482, T=0.452, P-value>0.6. In Sample 2, in male subjects: n=238, T=2.604, P-value=0.01, in female subjects: n=425, T=0.703, P-value> 0.4. On the combined study population (N=1,443), in male subjects: n=536, T=3.372, P-value=0.0008, permutation P-value=0.0010, in female subjects: n=907, T=0.811, P-value>0.4, a sensitivity analysis that excluded the 20.4% of subjects exposed to>1 childhood trauma : P-value=5.1-5e in males.	We observed an association between the C allele and total PT...... We observed an association between the C allele and total PTSD symptoms, as measured by PSS, in male subjects but not in female subjects. We next performed the same analysis in Sample 2 and again observed an association between the C allele and PSS score in male subjects but not female subjects. We performed all analyses on the combined study population (N=1,443), stratifying by sex. When we combined Samples 1 and 2 in a stratified analysis, we observed the same pattern in which the C allele was associated with PSS score in male subjects but not female subjects. This result was robust to a sensitivity analysis that excluded the 20.4% of subjects exposed to >1 childhood trauma. Even though trauma (as measured by the variable TEI) was a significant predictor of PSS score in our model (T=11.19), the significant association between genotype and PSS score remained. When including childhood trauma (as measured by the continuous CTQ variable) in our model, again the association between genotype and PSS score in males remained significant. More...	Significant
rs523349	Hyperarousal symptoms	SRD5A2	In males, n=535, T=3.151, P-value=0.0017, permutation P-value=0.0018; in females, P-value>0.3.	In males, we found a significant association with PTSD sympt...... In males, we found a significant association with PTSD symptom severity on all three PSS subscale scores, there were no associations with PSS subscales in females. More...	Significant

Gene * Environment result reported by this study (count: 4)

Marker	Phenotype	Related Gene	Environment	Statistical Values	Author Comments	Marker's Category
rs523349	Total PTSD symptoms	SRD5A2	Childhood trauma questionnaire (CTQ)	The interaction between SRD5A2 -V89L and CTQ: P-value=0.052.	The interaction between SRD5A2 -V89L and CTQ when predicting...... The interaction between SRD5A2 -V89L and CTQ when predicting PSS score in males was suggestive but not significant. More...	Non-significant
rs523349	Total PTSD symptoms	SRD5A2	Sex	Interaction between sex and genotype: N=1,443, T=3.206, P-value=0.0014.	We observed a significant interaction between sex and genoty...... We observed a significant interaction between sex and genotype, suggesting a sex-dependent association between SRD5A2-V89L and PSS. More...	Significant
rs523349	Proxy-diagnosis of PTSD	SRD5A2	Sex	Sex by genotype interaction: N=1,443, T=2.788, P-value=0.005.	We observed a significant sex by genotype interaction. We observed a significant sex by genotype interaction.	Significant
rs523349	Total PTSD symptoms	SRD5A2	Traumatic events inventory (TEI)	Interaction between SRD5A2 -V89L and TEI in males:P-value>0.1.	We did not observe an interaction between SRD5A2 -V89L and T...... We did not observe an interaction between SRD5A2 -V89L and TEI when predicting PSS score in males. More...	Non-significant