NAD (P) H Quinine Oxidoreductase (NQO1) as a Risk Modifier of Susceptibility to Polycythaemia Vera in Sudan

Abstract

Polycythaemia Vera (PV) is a clonal disorder characterized by overproduction of mature red blood cells in the bone marrow. Myeloid and megakaryocytic elements are also often increased. Although JAK2 gene mutations are the primary genetic abnormality in PV that has a direct association with the pathogenesis of the disease, many other genetic abnormalities have been reported to be a risk factor in PV. The aim of this study was to examine the association of NQO1 C609T polymorphism with the risk of PV and the clinical outcome among PV patients in Sudan. The study included 48 PV patients, their NQO1 C609T genotypes (PCR/RFLP) and haematological characteristics (Sysmex KX-21N) were determined and compared with 50 age and sex matched normal subjects as control. When the NQO1 609CC genotype was defined as the reference, a 3.1-fold increased risk of PV for those carrying NQO1 609CT (heterozygous) genotype was observed (OR 3.071, P value 0.028). No significant differences were observed in the mean Hb level, RBCS count and PCV between patients with mutant genotypes and those with wild type, this finding indicated that there is no association between NQO1 C609T polymorphism and the clinical outcome of PV. In conclusion, we examined the association between NQO1 C609T polymorphism and the risk of PV. Our results indicate that NQO1 C609T mutant genotypes with low enzymatic activity are associated with increased risk of PV.