The relationship between combat-related posttraumatic stress disorder and the 5-HTTLPR/rs25531 polymorphism

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.

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.

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).

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.