Evaluation of the Effect of <italic>NQO1 C609T (rs1800566)</italic> Gene Variations in Philadelphia-negative Myeloproliferative Neoplasms in Turkish Population

Abstract

Introduction:Philadelphia-negative myeloproliferative neoplasm (MPN) is a hematopoietic stem cell disorder consisting of essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) associated with myeloid cell proliferation without differentiation and maturation defects. It is characterized by hypercellular bone marrow and an increase in one or more cell lines in the peripheral blood. In the hematopoietic stem cell, janus kinase 2 (JAK2), which is a cytoplasmic tyrosine kinase, remains constantly phosphorylated (active) as a result of the V617F somatic mutation in the pseudokinase region. Even if the phosphorylated JAK2 does not receive a stimulus, it performs signal transmission and causes continuous gene expression. This explains the excessive increase in one or more blood cell lines. NAD(P)H quinone oxidoreductase-1 (NQO1) is a phase 1 enzyme that prevents the formation of reactive and toxic semiquinone metabolites by reducing two electrons in one step. The C609T polymorphism of the NQO1 gene leads to loss of enzyme activity due to the enzyme becoming unstable. While enzyme activity is not observed in individuals with both mutant alleles, moderate activity is observed in heterozygous individuals. Studies have reported a relationship between NQO1 C609T polymorphism and various cancer types. In our study, it was aimed to investigate the possible relationship between NQO1 C609T polymorphism and MPN development.Methods:Our study group consisted of 119 MPN patients and 122 healthy controls. DNA isolation was performed from peripheral blood taken from the study groups. The JAK2 V617F mutation was detected using Real-time polymerase chain reaction (PCR), and NQO1 C609T gene polymorphism was detected using the PCR- restriction fragment length polymorphism method. SPSS 21.0 was used for statistical analysis.Results:No statistically significant difference was found between the patient and control groups in terms of NQO1 genotype distributions (p>0.05). When cases with ET, PMF, and PV were compared in terms of frequency of JAK2 V617F mutation, the rate in PV was higher (respectively; 62.5%, 61.5%, 78.6%). There was no relationship between JAK2 mutation positivity and NQO1*2 polymorphism.Conclusion:According to the results obtained from our study, there is no relationship between NQO1*2 polymorphism and MPN. Variants of the NQO1 enzyme, which is essential in detoxification and activation of procarcinogens, did not increase the formation of the JAK2 V617F mutation, which is common in MPN patients. It is thought that the results should be supported by increasing the number of patient and control groups.

Keywords

• myeloproliferative neoplasm
• mpn
• jak2 v617f mutation
• nqo1 c609t gene polymorphism