The JAK2 gene encodes for a non‐receptor tyrosine kinase that plays a key role in the JAK/STAT signaling transfer pathway. Genetic polymorphisms of this gene have been indicated to be associated with myeloproliferative neoplasm‐associated thrombosis in recent studies. This research aimed to evaluate the association between the variant rs10974944 and different types of Myeloproliferative neoplasms disorders in the Vietnamese population. DNA samples were obtained from 172 essential thrombocythemia patients, 14 primary myelofibrosis patients, 76 polycythemia vera patients, and 192 healthy controls. The JAK2 rs10974944 and V617F genotypes were identified by the polymerase chain reaction‐restriction fragment length polymorphism genotyping and Sanger sequencing methods. Results showed that there was a strong association between rs10974944 and Myeloproliferative neoplasms phenotype (p < .0001) and the most significant association was observed in the recessive model of the mutant allele (G). The G allele carriers had a 1.74, 2.86, and 3.03 higher risk of getting essential thrombocythemia, primary myelofibrosis, and polycythemia vera, respectively. Interestingly, this effect of rs10974944 seemed to be independent of the JAK2 V617F genotype. The distribution of rs10974944 genotypes were significantly different between V617F‐positive and negative groups (p = .008). Moreover, the GG genotype of rs10974944 was observed to be associated with the risk of getting Myeloproliferative neoplasms both in JAK2 V617F‐positive group, and for the first time in JAK2 V617F‐negative patients. A systematic meta‐analysis in different populations strengthened the evidence regarding the correlation between rs10974944 and myeloproliferative neoplasm disorders. To sum up, our results suggested that rs10974944 can be used as a predisposition screening marker for predicting Myeloproliferative neoplasms susceptibility.
Polycythemia vera, essential thrombocythemia and primary myelofibrosis are members of the Philadelphia negative chronic subgroup of Myeloproliferative neoplasm. Published studies showed that the mutation JAK2 V617F is mostly responsible for the diseases; therefore, an accurate, low-cost and rapid molecular method to identify this mutation is important in screening and early diagnostic of these diseases. Different methods for genotyping of JAK2 V617F have been proposed. In this study, we evaluated the quality and cost-effectiveness of three genotyping methods, i.e., PCR-ARMS, PCR-RFLP, Sanger sequencing, to determine the appropriate genotyping for JAK2 V617F and predicted in silico the effect of this mutation on the structure and function of Janus kinase 2 protein. Results showed that the Sanger sequencing and PCR-RFLP genotyping methods were more accurate than PCR-ARMS. PCR-RFLP was also more rapid and economical than the other methods. In silico studies also demonstrated that the JAK2 V617F mutation had a large effect on the activity of corresponding protein. These results provided the initial data for further studies on genetic screening and prediction of myeloproliferative neoplasm and other related diseases in the Vietnamese population.
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