title: The relationship between combat-related posttraumatic stress disorder and the 5-HTTLPR/rs25531 polymorphism.
abstract: BACKGROUND
  Empirical evidence suggests that there is a significant genetic influence in the development of posttraumatic stress disorder (PTSD). The serotonin transporter (5-HTT) gene (SLC6A4) has been identified as a prime candidate for the development of the disorder, as 5-HTT is a working target for selective serotonin reuptake inhibitors (SSRIs), first line treatment agents for PTSD. Several studies have reported associations between 5-HTT-linked promoter region (5-HTTLPR) polymorphism variants and increased rates of PTSD in civilian samples. This study investigated the role of the 5-HTTLPR polymorphism, triallelically classified, in a sample of combat veterans with and without PTSD.
  
  
  METHODS
  Rates of PTSD were examined across three genotypes in a sample of 388 combat veterans. The short/long polymorphism of 5-HTTLPR and the A-G polymorphism within the 5-HTTLPR (rs25531) were genotyped, and statistical analyses were conducted.
  
  
  RESULTS
  There were significant intergroup (PTSD versus non-PTSD) differences in the genotype frequencies of 5-HTTLPR/rs25531 (χ(2) [1, n = 388] = 16.23, P = 5.62 × 10(-5) ). The 5-HTTLPR S'/S' (low transcriptionally efficient) genotype was also associated with the PTSD severity score in the 228 participants who had combat severity data (r = .15, P = 0.03).
  
  
  CONCLUSIONS
  The findings are consistent with previous research among civilian populations that have indicated that the low transcriptionally efficient S'/S' genotype of 5-HTTLPR is a risk factor for the development of PTSD after trauma exposure. Our findings are the first to examine this polymorphism and PTSD in a military sample. Additional large-scale investigations are needed to replicate these findings.
authors.affiliation: Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA. wanzh@musc.edu
authors.forename: Zhewu
authors.initials: Z
authors.lastname: Wang
authors.forename: Dewleen G
authors.initials: DG
authors.lastname: Baker
authors.forename: Judith
authors.initials: J
authors.lastname: Harrer
authors.forename: Mark
authors.initials: M
authors.lastname: Hamner
authors.forename: Matthew
authors.initials: M
authors.lastname: Price
authors.forename: Ananda
authors.initials: A
authors.lastname: Amstadter
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003130:Combat Disorders / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000235:genetics*; D014728:Veterans / Q000523:psychology*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins