Kan-İğne-Yaralanma Fobisindeki Vazovagal Senkopta Genetik Etiyolojinin Araştırılması

Abstract

Blood-injection-injury phobia is an important mental disorder considering its prevalence and its consequences. This disorder is differentiated from other specific phobias by the diphasic cardiovascular response and vasovagal syncope (VVS) observed during exposure to the phobic stimulus, and the apparent genetic predisposition in its etiology. Although there are separate studies on genetic predisposition in both blood-needle-injury phobia and VVS, studies on the genetic origin of VVS in blood-needle-injury phobia are limited. This study examined an individual and family member with a known history of VVS during exposure to blood, needles, injury, or medical interventions. DNA samples of two individuals positive for the aforementioned phenotype were evaluated by whole-exome sequencing (WES) method in this family, which was found to have patients with VVS in blood-needle-injury phobia in at least three generations. It is aimed to complete the variant filtering under the assumption of different inheritance patterns and to determine the common variant responsible for the disease in the family. In the study, first of all, genes and variants thought to be associated with these two conditions in previous genetic studies on blood-needle-injury phobia and VVS were screened in the WES data of two individuals. In addition, it was aimed to go to candidate variants by evaluating the WES data of two individuals and performing eliminations in accordance with some criteria. In the results of working; since a variant in the ADORA2A, COMT, BDNF genes previously studied in blood-needle-injury phobia and in the ADRB1, ADORA2A and GNAS1 genes previously studied in VVS were detected at least heterozygously in both affected individuals, it was thought that these variants may also contribute to the phenotype in this family. In addition, as a result of WES analysis, one common variant was detected in ST6GALNAC3, SLC6A13, LSAMP, KCNN3 genes in both individuals. In both individuals, cytosine nucleotide was substituted for adenine in the 669th position of the ST6GALNAC3 gene, adenine nucleotide was substituted for guanine at the 709th position of the SLC6A13 gene, and adenine nucleotide was substituted for cytosine at the 67th position of the LSAMP gene. In both individuals, triple AGC repeat was added between nucleotides 200 and 241 in the KCNN3 gene. Consequently, these four genes can be considered as candidate genes for VVS in blood-needle-injury phobia. As far as we know, there is no previous study on the role of these genes in blood-needle-injury phobia or VVS. Further studies are needed on the role of these genes and the proteins synthesized by these genes in the pathogenesis of VVS in blood-needle-injury phobia.