Molecular Biomarkers & Diagnosis

The Possibility of Applying a Combination of Allelic Variants of IL-1β Gene and WWC1 Gene for Assessing Susceptibility to PTSD (Pilot Investigation)

Abstract

Krasnov I, Klein O, Azab M, Mizruchin A and Izakson L

Memory and fear are two overlapping CNS processes in which mechanism of synaptic plasticity plays a key role. Fear increases likelihood fixation in memory behaviorally important information associated with a traumatic event. For healthy psychological functioning is crucial the ability to update the content and emotional charge of memories (cognitive plasticity) contributing to fading and extinction of fear memories once this event has been passed. Memory performance and its plasticity are associated with ability of synapses to change of number α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR) on the post-synaptic membrane surface. AMPAR undergo exocytosis/endocytosis (AMPAR trafficking), thus changing the strength of neural connections (synaptic plasticity) and contributing to formation, maintaining and transformation of memories. Impairment of AMPAR trafficking may become a cause of deficiency of fear extinction, and development of posttraumatic stress disorder (PTSD). AMPAR trafficking is controlled by the nervous and the immune systems jointly. Kidney and brain expressed protein (KIBRA) and interleukin (IL) -1β are important regulators of AMPAR trafficking. Data show that genes encoding of these proteins (KIBRA-WWC1 gene and IL-1β gene) and their alleles mediates of stress impact on synaptic plasticity and are a bridge between memory and diseases. Disease susceptibility in humans is most commonly associated with single nucleotide polymorphisms (SNPs), when corresponding sequences of DNA from different individuals differ at one DNA base. PTSD is polygenic disorder, so can be identified the combination of allelic variations of SNPs, associated with strength and plasticity of memory that distinguish PTSD patients from the control. Our preliminary results showed that the combination of the certain allelic variants of WWC1, SNP rs17070145 (T/C), and the IL-1β gene, SNP rs16944 (A/G), is characteristic for PTSD compared to depressive and healthy groups. We assume that this combination might be used for pre-clinical diagnosis PTSD and in clinical practice.