Role of NQO1 gene involvement and susceptibility of T2DM among Saudi Arabia population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia. As a significant contributor to the development and progression of diabetes.Oxidative stress has been linked to a number of symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, present research work aimed to evaluate the genetic abnormality of NQO1 gene polymorphism, expression and vitamin-D level assessment among the T2DM patients. Present research study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy control. Total RNA was extracted from the whole blood using the Trizol method and further cDNA was synthesized and expression was evaluated. Significant difference in NQO1 genotypes distribution among the T2DM patients and healthy controls (p=0.04). Compared to NQO1 CC wild type genotype, NQO1 CT heterozygous genotype had odds ratio of 1.96 (1.08-3.55), and NQO1 TT mutant type genotype had odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p<0.0001) and homozygous mutant TT genotype (p=0.0004), compared to homozygous wild type CC genotype. NQO1 mRNA expression level was also compared with respect to vitamin-D level among the T2DM patients. T2DM patients with vitamin-D deficiency had 1.83 fold NQO1 mRNA expression while vitamin-D insufficient and sufficient T2DM cases had 3.31 fold (p<0.0001) and 3.70 fold (p<0.0001) NQO1 mRNA expression. Results concluded that NQO1 (C609T) CT and TT genotypes played significant role in worseness of type II diabetes mellitus and decreased expression of NQO1 mRNA expression could be important factor for disease worseness as well as hypermethylation could be factor for decreased expression leading to disease severity. As the decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype as well as associated with vitamin-D deficiency may contribute to disease progression.