The role of memory-related gene WWC1 (KIBRA) in lifetime posttraumatic stress disorder: Evidence from two independent samples from african conflict Regions

摘要

Background: Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD. Methods: Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample. Results: An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p =.007, odds ratio =.29 [95% confidence interval =.15-.54]). This effect was confirmed in the independent Ugandan sample. Conclusions: This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories.