Table 1. Frequency of actionable pharmacophenotypes in Hong Kong Chinese.
| Gene | Allele | Actionable phenotype | Genotype definition | Frequency (%) | |
|---|---|---|---|---|---|
| by phenotype | by gene | ||||
| CYP2C19 | No function: *2, *3, *6 | Intermediate metabolizer | One normal function allele and one no function allele | 45.25 | 57.21 |
| Poor metabolizer | Two no function alleles | 11.96 | |||
| CYP3A5 | Functional allele: *1 | Extensive metabolizer | Two functional alleles | 6.13 | 43.38 |
| Intermediate metabolizer | One functional allele and one nonfunctional allele | 37.25 | |||
| CYP2B6 | Decreased function: *6 | Intermediate metabolizer | One normal function allele and one decreased function allele | 35.28 | 40.51 |
| Poor metabolizer | Two decreased function alleles | 5.23 | |||
| CYP4F2 | rs2108622 | Carrier of decreased function allele | Carrier of rs2108622 T allele | 39.89 | 39.89 |
| HLA-B | *15:02, *57:01, *58:01 | *15:02 positive | Heterozygous or homozygous for HLA-B*15:02 | 18.42 | 33.88 |
| *57:01 positive | Heterozygous or homozygous for HLA-B*57:01 | 0.18 | |||
| *58:01 positive | Heterozygous or homozygous for HLA-B*58:01 | 17.04 | |||
| SLCO1B1 | rs4149056 | Intermediate function | TC genotype at rs4149056 | 23.89 | 25.81 |
| Low function | CC genotype at rs4149056 | 1.92 | |||
| NUDT15 | No function: *2, *3 | Intermediate metabolizer | One normal function allele and one no function allele | 17.63 | 18.58 |
| Poor metabolizer | Two no function alleles | 0.95 | |||
| IFNL3 | rs12979860 | Unfavorable response genotype | Carrier of rs12979860 T allele | 13.57 | 13.57 |
| CYP2D6 | Duplication of functional allele: *1x2, *1x3, *2x2, *2x3 | Ultrarapid metabolizer | Carrier of duplications of functional alleles | 3.3 | 12.24 |
| Reduced function: *10, *10x2, *14B, *36-*10, (*36-*10)x2, *41 | |||||
| No function: *4, *5, *6, *14A, *36, *36x2 | Intermediate metabolizer | One decreased function and one no function allele |
8.54 | ||
| Poor metabolizer | Two no function alleles | 0.4 | |||
| CYP2C9 | No function: *3 | Intermediate metabolizer | One normal function allele and one no function allele | 5.32 | 5.39 |
| Poor metabolizer | Two no function alleles | 0.07 | |||
| UGT1A1 | Decreased function: *6, *28, *37 | Poor metabolizer | Two decreased function alleles | 5.08 | 5.08 |
| TPMT | No function: *3A, *3C | Intermediate metabolizer | One normal function allele and one no function allele | 2.92 | 2.94 |
| Poor metabolizer | Two no function alleles | 0.02 | |||
| HLA-A | *31:01 | *31:01 positive | Heterozygous or homozygous for HLA-A*31:01 | 2.48 | 2.48 |
| G6PD | WHO class II-III: KaiPing, Canton, Gaohe, Chinese-5, Hechi, Maewo, Quing Yan | Deficient (male) | One deficient (class II–III) allele | 3.68 | 3.68 |
| Deficient (female) | Two deficient (class II-III) alleles | 0.14 | 0.14 | ||
| CFTR | rs115545701, rs78655421 | Favorable response genotype | Homozygous or heterozygous for CFTR variants listed in the FDA-approved drug label | 0.09 | 0.09 |
In this study, 15 pharmacogenes were found to have actionable pharmacogenetic variants. The frequency of actionable phenotypes was derived based on the Hardy-Weinberg equation, except for CYP2D6 where the frequency was retrieved from a published Hong Kong study by Chan et al.25
N/A, not applicable.