TABLE 2.
Phenotype and diplotype frequencies of 12 pharmacogenes in the study population by ancestry
| Gene | Phenotype | Diplotype | European American n (%)a |
African American n (%)a |
|---|---|---|---|---|
| CYP2C9 | Extensive metabolizer | *1/*1 | 433 (64.2) | 162 (92.6) |
| Intermediate metabolizer | *1/*2, or *1*3 | 213 (31.6) | 13 (7.4) | |
| Poor metabolizer | *2/*2, *3/*3, *2/*3 | 28 (4.2) | 0 (0.0) | |
| CYP2C19 | Ultra-rapid metabolizer | *17/*17 | 28 (4.1) | 7 (4) |
| Rapid metabolizer | *1/*17 | 189 (27.9) | 48 (27.6) | |
| Extensive metabolizer | *1/*1 | 257 (37.9) | 62 (35.6) | |
| Intermediate metabolizer | *1/*2, *1/*3, or *2/*17 | 186 (27.4) | 52 (29.9) | |
| Poor metabolizer | *2/*3, *2/*2, or *3/*3 | 17 (2.5) | 5 (2.9) | |
| CYP3A5 | Extensive metabolizer | *1/*1 | 4 (0.6) | 35 (20.1) |
| Intermediate metabolizer | *1/*3, *1/*6, or *1*7 | 74 (11.0) | 91 (52.0) | |
| Poor metabolizer | *3/*3, *6/*6, *7/*7, *3/*7, *3/*6, or *6/*7 | 597 (88.4) | 48 (27.6) | |
| CYP4F2 | Normal function | *1/*1 | 339 (55.2) | 132 (75.4) |
| Intermediate function | *1/*3 | 275 (4.8) | 38 (21.7) | |
| Decreased function | *3/*3 | 64 (10.4) | 5 (2.9) | |
| DPYD | Normal metabolizer | Activity Score: 2 | 627 (92.5) | 173 (98.7) |
| Intermediate metabolizer | Activity Score: 1-1.5 | 40 (5.9) | 2 (1.1) | |
| Poor metabolizer | Activity Score: 0-0.5 | 1 (0.1) | 0 (0.0) | |
| F5 | Normal risk | C/C | 637 (94.0) | 175 (100) |
| High risk for thromboembolism | C/T | 40 (6.0) | 0 (0.0) | |
| Higher risk for thromboembolism | T/T | 1 (0.1) | 0 (0.0) | |
| HLA-B*57:01 | Very low risk for hypersensitivity | *X/*X | 633 (93.4) | 171 (97.7) |
| High risk for hypersensitivity | *57:01/*X, or *57:01/*57:01 | 45 (6.6) | 4 (2.3) | |
| IFNL3 | Increased response | CC | 301 (44.4) | 28 (16.0) |
| Decreased response | CT or TT | 377 (55.6) | 147 (84.0) | |
| NUDT15b | Normal metabolizer | *1/*1 | 675 (99.7) | 172 (99.4) |
| Intermediate metabolizer | *1/*3 | 2 (0.3) | 1 (0.6) | |
| Poor metabolizer | *3/*3 | 0 (0.0) | 0 (0.0) | |
| SLCO1B1 | Normal function | *1a/*1b, *1a/*1a, or *1b/*1b | 478 (70.5) | 162 (92.6) |
| Intermediate function | *1a/*15, *1a/*17, *1b/*15, *1b/*17, *1a/*5, or *1b/*5 |
190 (28.0) | 13 (7.4) | |
| Low function | *5/*5, *5/*15, *5/*17, *15/*15, *15/*17, or *17/*17 | 10 (1.5) | 0 (0.0) | |
| TPMTc | Normal, high activity | *1/*1 | 600 (88.8) | 160 (91.4) |
| Intermediate activity | *1/*2, *1/*3A, *1/*3B, or *1/*3C | 73 (10.8) | 14 (8.0) | |
| Low activity | *3A/*3A, *2/*3A, *3C/*3A, or *3C/*2 | 2 (0.3) | 1 (0.6) | |
| VKORC1 | Low warfarin sensitivity | GG | 237 (35.0) | 139 (79.9) |
| Intermediate warfarin sensitivity | AG | 337 (49.7) | 32 (18.3) | |
| Warfarin sensitive | AA | 104 (15.3) | 3 (1.7) |
Abbreviations: CYP, cytochrome P450; DYPD, dihydropyrimidine dehydrogenase; F5, Factor V Leiden; HLA, major histocompatibility complex;IFN, interferon; NUDT, nudix hydrolase; SLCO, solute carrier organic anion transporter; TPMT, thiopurine S-methyltransferase; VKORC1, vitamin K epoxide reductase complex 1.
a
Phenotypes may not add up to 100% due to inconclusive alleles or missing phenotypes in some individuals.
b
NUDT15*2 is a rare variant and not included due to unavailability on the GWAS panel.
c
TPMT *4 is a rare variant and not included due to unavailability on the GWAS panel.