Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

“…Subjects with the TT genotype have no detectable NQO1 protein, and those with the CT genotype have intermediate levels of NQO1 protein. Vascular endothelium from subjects with the CC genotype show NQO1 enzymatic activity by immunostaining, whereas subjects with the CT genotype show decreased activity and those with the TT genotype show no activity [8]. Furthermore, a recent report demonstrates an association between NQO1 polymorphism and the inflammatory response in cardiopulmonary bypass [18].…”

“…A homozygous mutation results in a complete loss of NQO1 protein and enzymatic activity. Therefore, a mutation at this locus could increase susceptibility to oxidative stress [2,8]. This NQO1 polymorphism has been reported to have an additive effect on oxidative damage, thus manifesting a biological significance for cancer susceptibility and chemoprotection [3,8].…”

Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) Genes in Thai Cervical Cancer Patients with HPV 16 Infection

“…The NQO1 gene (rs1800566) TT genotype is associated with a null anticancer enzyme activity and may affect cancer development through the reduction cytotoxic agents containing the quinone moiety into hydroquinone individuals with lung, bladder and colorectal cancer (Siegel et al, 1999). The allele frequency of the T allele is depending on specific ethnic groups such as 0.217 in Caucasians and 0.398 in Japanese.…”

“…However, this polymorphism is variable in different ethnic groups with 20% in Asians and 2-5% in Caucasians and Africans (Kelsey et al, 1997). The variant T allele has been associated with reduction of NQO1 enzymatic activity with homozygotes (TT) devoid of NQO1 activity while the wild-type homozygotes (CC) display the highest enzymatic activity (Siegel et al, 1999). The T allele has been associated with increased risk of several solid tumors (Chao et al, 2006) such as colorectal cancer (Schulz et al, 1997) and urological malignancies (Lafuente et al, 2000).…”

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

“…A number of single nucleotide polymorphisms (SNPs) have been discovered in this gene (Nebert et al, 2002), of which rs1800566 polymorphism, a C-to-T transition at nucleotide position 609 in exon 6, has been studied by various researchers. Genotype-phenotype studies demonstrated that this kind of polymorphism is associated with a decreased activity of NQO1 enzymatic activity and shows a phenotypic gene-dose effect (Siegel et al, 1999;Basu et al, 2004;Ross et al, 2004). Because of this SNP's functional consequence, many case-control studies were conducted to evaluate the association of NQO1 rs1800566 polymorphism with bladder cancer risk.…”