Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms.

Cytochrome P450 (CYP) 2C8 and 2C9 are polymorphic enzymes. The CYP2C83 and CYP2C92 are the major variant alleles in Caucasian populations. The enzymes encoded by these variant alleles have impaired function for the metabolism of several drug substrates. In the present study 1468 subjects that were used as population-based controls in the Stockholm Heart Epidemiology Program (SHEEP) were genotyped by allelic discrimination using a 5'-nuclease assay for CYP2C81, 2C83, 2C91, 2C92, and 2C93 variant alleles in which the frequencies appeared to be 0.91, 0.095, 0.83, 0.11, and 0.066, respectively. Approximately, 96% of the subjects with CYP2C83 allele also carried a CYP2C92 and 85% of the subjects that had CYP2C92 variant also carried a CYP2C83. The number of subjects carrying both of the CYP2C813 and CYP2C91*2 was 4.5-fold higher than expected. This strong association may be of importance especially for the metabolism of common substrates of CYP2C8 and CYP2C9 like arachidonic acid that produces physiologically active metabolites.