Serotonin Transporter Gene (SLC6A4) Promoter Polymorphisms and the Susceptibility to Posttraumatic Stress Disorder in the General Population

Objective: There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample. Method: Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM–IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped. Results: Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L _A alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L _A /L _A genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L _A allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L _A allele. Conclusions: An additive gene-environment interaction with the high expression L _A allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L _A allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure.