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 (χ²[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. Depression and Anxiety, 2011.