NAD(P)H:quinone oxidoreductase: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations.
NAD(P)H:quinone oxidoreductase (NQO1) catalyses the two-electron reduction of quinone compounds. NQO1 is involved in the reductive bioactivation of cytotoxic antitumour quinones such as mitomycin C, but also plays a protective role against the carcinogenicity and mutagenicity of quinones, their precursors and metabolites. Three alleles have been identified in the human population: the functional Arg139/Pro187 allele (which we have termed NQO1*1); the nonfunctional allele Arg139/Ser187 (NQO1*2) and the Trp139/Pro187 allele (NQO1*3), which is associated with a diminished activity. We applied polymerase chain reaction-based genotyping assays to characterize interethnic variability in the frequency of NQO1 alleles in Caucasian (n = 575), Canadian Native Indian (n = 110), Canadian Inuit (n = 83) and Chinese (n = 86) populations. The NQO1*2 allele was found at significantly higher frequencies in Chinese (0.49) and Native North American populations (Inuit 0.46; Canadian Native Indians 0.40) compared with Caucasians (0.16). The NQO1*3 allele was not observed in Inuit individuals, and occurred at a lower frequency than the NQO*2 allele in Caucasians (0.05), Chinese (0.04) and Canadian Native Indians (0.01). Our results predict that a greater proportion of Orientals and related ethnic groups lack, or have reduced, NQO activity relative to Caucasians. Affected individuals may not only exhibit resistance to quinone-based cancer therapy because of a decreased production of cytotoxic drug metabolites, but may also be more susceptible to toxicities associated with toxicants.
Gaedigk
A
A
Section of Pediatric Clinical Pharmacology and Experimental Therapeutics, The Children's Mercy Hospital, Kansas City, Missouri 64108, USA. agaedigk@cmh.edu
Tyndale
R F
RF
Jurima-Romet
M
M
Sellers
E M
EM
Grant
D M
DM
Leeder
J S
JS
D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002170:Canada; D002681:China / Q000208:ethnology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D009626:Terminology as Topic; D044465:White People / Q000235:genetics
D016660:NAD(P)H Dehydrogenase (Quinone)