Table 1.
Translation of genotype to predicted phenotype for CYP2C19 and CYP2D6.
| Gene | Examples of diplotypes | Genotypes | Predicted phenotypes |
|---|---|---|---|
| CYP2C19 | *1/*1, *1/*17 | Two normal function alleles or one normal function and one increased function allele. | Normal metabolizer |
| *1/*2, *1/*3, *2/*17, *3/*17 | One no or decreased function allele in combination with either one normal function allele or one increased function allele. | Intermediate metabolizer | |
| *2/*2, *2/*3, *3/*3 | Two no or decreased function alleles. | Poor metabolizer | |
| *17/*17 | Two increased function alleles. | Ultrarapid metabolizer | |
| CYP2D6 | *1/*1, *1/*41, *1/*41×3a | Gene doseb 1.5–2.5 | Normal metabolizer |
| *1/*4, *41/*41, *4/*41 | Gene doseb 0.5–1 | Intermediate metabolizer | |
| *4/*4, *4/*5 | Gene doseb 0 | Poor metabolizer | |
| *1/*1×2, *1/*2×2, *2×3/*4, *1/*41×4a | Gene doseb ≥ 3 | Ultrarapid metabolizer |
The *-alleles mentioned in the table above are characterized by the following sequence variations:
CYP2C19*1: defined as the allele without variations affecting enzyme activity (in clinical practice as the allele without any of the determined variations).
CYP2C19*2: rs-number: rs12769205 and rs4244285; NC_000010.11(NM_000769.2): c.[332-23 A > G; 681 G > A]; NC_000010.11: g.[94775367 A > G; 94781859 G > A].
CYP2C19*3: rs-number: rs4986893; NM_000769.2: c.636 G > A; NP_000760.1: p.(Trp212*); NC_000010.11: g.94780653 G > A.
CYP2C19*17: rs-number: rs12248560; NM_000769.2 c.−806C > T; NP_000760.1: p.(Ile331Val); NC_000010.11: g.94761900 C > T.
CYP2D6*1: defined as the allele without variations affecting enzyme activity (in clinical practice as the allele without any of the determined variations).
CYP2D6*2: rs-numbers: rs16947 and rs1135840; NM_000106.6: c.[886 C > T; 1457 G > C]; NP_000097.3: p.(Arg296Cys; Ser486Thr); NC_000022.11: g.[42127941 G > A; 42126611 C > G].
CYP2D6*4: rs-number: rs3892097; NG_008376.3(NM_000106.6): c.506-1 G > A; protein sequence not available; NC_000022.11: g.42128945 C > T.
CYP2D6*5: CYP2D6 full gene deletion.
CYP2D6*41: rs-numbers: rs16947, rs28371725 and rs1135840; NG_008376.3(NM_000106.6): c.[886 C > T; 985 + 39 G > A; 1457 G > C]; NP_000097.3: p.(Arg296Cys; protein sequence not available; Ser486Thr); NC_000022.11: g.[42127941 G > A; 42127803 C > T; 42126611 C > G].
ax2 denotes a gene duplication, x3 a gene triplication and x4 a gene quadruplication.
bThe gene dose is 1 for an allele encoding a fully functional enzyme, 0.5 for an allele encoding a reduced activity enzyme and 0 for an allele encoding an inactive enzyme.