LINKAGE DISEQUILIBRIUM BETWEEN CYP2C SINGLE NUCLEOTIDE POLYMORPHISMS IN A HEALTHY SCANDINAVIAN POPULATION

The human cytochrome P450 2C subfamily consist of the important drug metabolizing enzymes CYP2C8, CYP2C9 and CYP2C19 encoded from genes with genetic polymorphisms affecting drug metabolism. 396 healthy Scandinavian volunteers were genotyped for the pharmacological important CYP2C allelic variants: CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*17. Genotype- and allele frequencies were calculated and linkage disequilibrium parameters were determined and CYP2C haplo- and diplotypes were inferred.
CYP2C19*17 was in linkage disequilibrium with the six other tested polymorphisms. Ten CYP2C haplotypes were inferred of which the CYP2C wildtype was most frequent (47%). The second most frequent haplotype (18%) is composed by CYP2C19*17 and CYP2C8 and CYP2C9 wildtype alleles. Four rare CYP2C8*2 allele was fund which was all inferred in haplotype with CYP2C19*17. CYP2C19*17 is a frequent allelic variant in linkage disequilibrium with pharmacological important CYP2C8 and CYP2C9 alleles.