Objective: The aim of this study was to predict the functional impact of pathogenic mutations and the mRNA expression profiles of the platelet endothelial aggregation receptor 1 (PEAR1), protein S (alpha) (PROS1), and adrenoceptor alpha 2A (ADRA2A) genes in deep vein thrombosis (DVT), as well as to examine the effects of these genes on the pathogenesis of DVT.
Materials and Methods: Patients diagnosed with DVT were selected for the study and healthy individuals were used as con-trols. Mutations in the PEAR1, PROS1, and ADRA2A genes were determined by DNA sequencing analysis and gene expres-sions were determined using quantitative real-time polymerase chain reaction testing. Polymorphism Phenotyping v2 (Poly-phen-2; http: //genetics.bwh.harvard.edu/pph2/), SNAP2 (https: //rostlab.org/services/snap2web/) and MutationTaster (https: //www.mutationtaster.org/) software were used to define the pathogenic effects of mutations detected by sequencing the selected genes in hotspot regions. Mutation and gene expression analyses were noted in the results and clinical data.
Results: A total of 27 patients with DVT and 10 healthy individuals were included in the study. Twenty-one mutations were detected in the 27 patients, most often in the PROS1 gene. A p.Ala303Val mutation is located on the human sex hormone-binding globulin (SHBG) domain of mutation PROS1 and is pathogenic. A p.A303V mutation is associated with premature termination in codon 303 of the SHBG domain. Examination of the effect on the mRNA expression level of wild-type versus mutant genotypes revealed that the mutant PROS1 p.A303V expression was significantly lower (p=0.041).
Conclusion: A p.A303V mutation in PROS1 might be an independent risk factor for DVT, which could provide helpful insight into the pathogenesis of DVT.