NAD(P)H-QUINONE OXIDOREDUCTASE - POLYMORPHISMS AND ALLELE FREQUENCIESIN CAUCASIAN, CHINESE AND CANADIAN NATIVE INDIAN AND INUIT POPULATIONS

NAD(P)H:quinone oxidoreductase (NQO1) catalyses the two-electron reduc tion of quinone compounds. NQO1 is involved in the reductive bioactiva tion of cytotoxic antitumour quinones such as mitomycin C, but also pl ays a protective role against the carcinogenicity and mutagenicity of quinones, their precursors and metabolites. Three alleles have been id entified in the human population: the functional Arg139/Pro187 allele (which we have termed NQO11); the nonfunctional allele Arg139/Ser187 (NQO12) and the Trp139/Pro187 allele (NQO1*3), which is associated wi th a diminished activity. We applied polymerase chain reaction-based g enotyping assays to characterize interethnic variability in the freque ncy of NQO1 alleles in Caucasian (n = 575), Canadian Native Indian (n = 110), Canadian Inuit (n = 83) and Chinese (n = 86) populations. The NQO12 allele was found at significantly higher frequencies in Chinese (0.49) and Native North American populations (Inuit 0.46; Canadian Na tive Indians 0.40) compared with Caucasians (0.16). The NQO13 allele was not observed in Inuit individuals, and occurred at a lower frequen cy than the NQO2 allele in Caucasians (0.05), Chinese (0.04) and Cana dian Native Indians (0.01). Our results predict that a greater proport ion of Orientals and related ethnic groups lack, or have reduced, NQO1 activity relative to Caucasians. Affected individuals may not only ex hibit resistance to quinone-based cancer therapy because of a decrease d production of cytotoxic drug metabolites, but may also be more susce ptible to toxicities associated with toxicants. Pharmacogenetics 8:305 -313 (C) 1998 Lippincott-Raven Publishers.