Cytochrome P4502C9 (CYP2C9) Genotypes in a Nordic Population in Denmark

The human CYP2C is a subfamily of P450 enzymes that metabolize approximately 20% of clinically used drugs (Goldstein 2001). The four members of the subfamily are: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 is an enzyme of major importance in human drug metabolism. Substrates for CYP2C9 include phenytoin (Banpai et al. 1996), S-warfarin (Rettie et al. 1992), acenocoumarol (Verstuyft et al. 2003a), losartan (Stearns et al. 1995), tolbutamide (Miners & Birkett 1996), glipizide (Kidd et al. 1999), fluvastatin (Kirchheiner et al. 2003) and some NSAIDs (Miners & Birkett 1998). Six different human CYP2C9 cDNA sequences have been reported to make the enzyme polymorphic (Stubbins et al. 1996). Since the wildtype CYP2C9*1 and the single nucleotide polymorphisms CYP2C9*2 and CYP2C9*3 were discovered first, they have undergone more thorough investigation showing that the allelic variants CYP2C9*2 and CYP2C9*3 encode enzymes with decreased substrate turnover (Craig et al. 2002; Kirchheiner et al. 2002; Shon et al. 2002). The CYP2C9*2 allele, which is derived from a C430»T single nucleotide polymorphism in exon 3, encodes the Arg144»Cys substitution, whereas a A1075»C single nucleotide polymorphism in exon 7 results in the substitution Ile359»Leu for CYP2C9*3 (Stubbins et al. 1996). The allele frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 and the genotype frequencies of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/ *3 and CYP2C9*3/*3 for a Nordic population in Denmark were determined. Two hundred seventy-six healthy Nordic (mainly Danish) volunteers of Caucasian origin were enrolled in the study. The 154 males and 122 females aged 19–42 were primarily students at the University of Southern Denmark. The pro