Elsevier

The Lancet

Volume 336, Issue 8714, 1 September 1990, Pages 529-532
The Lancet

Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification

https://doi.org/10.1016/0140-6736(90)92086-WGet rights and content

Abstract

A method for genotyping poor metabolisers of debrisoquine is based on specific polymerase chain reaction (PCR) amplification of parts of mutant genes for hepatic cytochrome P450IID6. Analysis by restriction fragment length polymorphism allowed identification of only 25% of poor metabolisers, but when it was combined with allele-specific PCR over 95% of poor metabolisers could be identified. The PCR method also allowed the identification of heterozygous carriers of mutant alleles.

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      Soon after the study on debrisoquine metabolism in lung cancer patients, the CYP enzyme responsible for metabolism of debrisoquine and sparteine, now referred to as CYP2D6, was purified from human liver (Distlerath et al., 1985), followed by isolation of cDNA clones and mapping to chromosome 22 (Gonzalez et al., 1988). Subsequent genome mapping and cDNA sequencing enabled the identification of the main polymorphisms associated with absence of activity and development of genotyping assays to detect poor metabolizers (Daly, Armstrong, Monkman, Idle, & Idle, 1991; Gaedigk, Blum, Gaedigk, Eichelbaum, & Meyer, 1991; Gough et al., 1990; Hanioka, Kimura, Meyer, & Gonzalez, 1990; Heim & Meyer, 1990; Kagimoto, Heim, Kagimoto, Zeugin, & Meyer, 1990). These developments enabled the findings on lung cancer susceptibility obtained using debrisoquine phenotyping to be followed up in larger populations.

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