The NQO1 gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a flavoprotein, which forms a homodimer and reduces quinones to hydroquinones. The NQO1 protein is expressed in human epithelial and endothelial tissues and at high levels throughout many human solid tumors. It is mainly a cytosolic enzyme, although it has also been localized in smaller amounts to mitochondria, endoplasmic reticulum, and nucleus. NQO1 is induced by oxidative stress, dioxin, and polycyclic aromatic hydrocarbons.
The NQO1 protein protects cells against radiation and chemical-induced oxidative stress. NQO1 was also acts as a p53 stabilizer and plays an important role in the protection against carcinogenic catechol estrogens. Disruptions of NQO1 protein have been associated with tardive dyskinesia (TD), an increased risk of hemeatotoxicity after exposure to benzene, and susceptibility to various forms of cancer.
The NQO1 gene is located on chromosome 16q22.1; it spans approximately 17 kb and has six exons. The NQO1 gene has been associated with detoxification of numerous endogenous and foreign compounds; it seems likely that the lack of NQO1 activity might increase the risk of certain types of toxicity and cancer. To date, there are 22 reported single-nucleotide polymorphisms (SNPs) in the NQO1 gene. The NQO1*1 allele codes for normal NQO1 enzyme and activity, while the NQO1*2 allele encodes a nonsynonymous mutation (p.P187S) that has negligible NQO1 activity.
[See: Saudi Arabia > Bu et al., 2004].
Bu et al. (2004) studied the frequencies of alleles and genotypes for CYP1A1, NAT2, GSTs, MTHFR, MTR (MS), and NQO*1 genes among Arabs. Of the studied group, 95% were from Saudi Arabia, and 5% were from Jordan, Syria, Lebanon, and Yemen. The mean age was 37 years, and male to female ratio was (25:1). Allele frequency for the NQO*1 C609T variant was 24% in the studied Arab group.
Ouerhani et al. (2013) conducted a case-control study to assess the impact of CYP1A1*2A (CYP1A1 T6235C); NQO1*2 (NQO1 C609T); TPMT*2 (TPMT G238C) and TPMT A719G polymorphisms on the risk of developing ALL. The frequencies of TPMT*2, TPMT A719G, NQO1*2, and CYP1A1*2 variants were examined in 100 patients with ALL and 106 healthy controls. The NQO1 609CT genotype was overrepresented in patients and was associated with an aggravating effect compared to the reference group with the NQO1 609CC genotype (p = 0.028, OR = 1.41; CI 95%: 1.04-1.93). The TPMT*2, TPMT 719*G, and CYP1A1*2 variants did not appear to influence ALL susceptibility (p > 0.05).