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 post- traumatic 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 (5)/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 life-time prevalence of PTSD was 26%, 35%, and 4.3% for those with zero, one, and two LA alleles, respectively, but the life- time 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 LA/LA genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 33. Thus, the odds ratio for PTSD in LA allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the LA allele. Conclusions: An additive gene-environment interaction with the high expression LA allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all LA allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure. [ABSTRACT FROM AUTHOR]