PEAR۱ genetic variants in Essential Thrombocythemia: The prevalence and association with hematological parameters and ET mutations

Backgrounds: Essential thrombocythemia (ET) is a type of myeloproliferative neoplasmcharacterized by the expansion of the megakaryocytic/platelet line. Given the undeniable role ofgenetic variations in the pathogenesis of ET, as well as the proven effects of PEAR۱ SNPs onplatelet function, the innovative purpose of this study is to investigate the prevalence of PEAR۱variants (rs۱۲۰۴۱۳۳۱ and rs۱۲۵۶۶۸۸۸) and their relationship to hematological parameters andET-related mutations.Materials and Methods: We studied ۱۰۵ ET patients and analyzed ET patients' mutationalprofiles, including JAK۲ V۶۱۷F mutation (detected by Allele-specific PCR), CALR, and MPLmutations (both through PCR amplification). Two SNPs of the PEAR۱ gene were assessedthrough ARMS-PCR, and the Sanger method was used for the validation of ARMS-PCRamplification.Results: The prevalence of rs۱۲۰۴۱۳۳۱ and rs۱۲۵۶۶۸۸۸ in ET patients were ۴۳.۹% and ۳۸.۵%,respectively, and rs۱۲۰۴۱۳۳۱ was significantly associated with increased platelet counts (PValue:۰.۰۲). As expected, the incidence of thrombotic events in JAK۲ + patients was high andsignificantly associated with JAK۲ mutation (P-Value: ۰.۰۲). The prevalence of thromboticevents was also high in patients with the rs۱۲۰۴۱۳۳۱ variant. Besides, a significant relationshipwas also found between the rs۱۲۰۴۱۳۳۱ and CALR mutation (P-Value: ۰.۰۳).Conclusion: In recent years, the footprint of the PEAR۱ variant's effect on platelet aggregationled to evaluating these variants in ET patients. Finally, the significant relationship between thers۱۲۰۴۱۳۳۱ variant and increased platelet count and CALR mutation announced that the idea ofthis study could be pursued and challenged in the future.

کلیدواژه ها:

Essential Thrombocythemia ، Platelet endothelial aggregation receptor ۱ ، Polymorphisms ، Platelet ، Janus kinase ۲ ، ARMS-PCR ، Prevalence