Table 1.
Actionable genotype/diplotype frequencies of clinically important pharmacogenes in the Qatari population.
| Gene | Examples of Affected drugs/category of drugs with clinical guidelines | Number of Variants analysed, Number of star alleles analysed | Major Actionable Genotypes/Diplotypes in the population, present in at least 5 individuals in the dataset | Phenotypic effect warranting change in drug, drug dose or drug monitoring | Number of individuals with actionable genotypes/diplotypes in the Qatari population (%) | Total Number of individuals with actionable genotypes/diplotypes in the Qatari population (%) | Total Number of individuals with actionable genotypes/diplotypes in the thousand genome populations (%) |
|---|---|---|---|---|---|---|---|
| CACNA1S | Potent Volatile Anesthetic Agents, Succinylcholine | 2 | (rs772226819 TT (c.520 C > T), rs1800559 AA (c.3257 G > A)) | Malignant Hyperthermia Susceptibility | 0 (0) | 0 | 0 |
| CYP2B6 | Efavirenz | 63, 38 | *6/*6, *6/*18, *6/*36 | Poor metabolizer | 497 (8.22) | 2781 (46.0) | 1295 (51.72) |
| *1/*6, *2/*6, *6/*22, *4/*6, *1/*18, *1/*36, *1/*9, *2/*9 | Intermediate metabolizer | 2284 (37.78) | |||||
| CYP2C9 | Phenytoin, NSAIDs | 94, 71 | *1/*2, *1/*3, *2/*2, *1/*11, *2/*11, *2/*9, | Intermediate metabolizer | 1832 (30.31) | 1931 (31.94) | 588 (23.48) |
| *2/*3, *3/*3 | Poor metabolizer | 99 (1.64) | |||||
| CYP2C19 | Clopidogrel, Voriconazole, Antidepressants, Proton Pump Inhibitors | 71, 39 | *1/*17 | Rapid metabolizer | 1804 (29.84) | 3509 (58.05) | 1483 (59.23) |
| *17/*17 | Ultrarapid metabolizer | 395 (6.53) | |||||
| *2/*2, *2/*35 | Poor metabolizer | 113 (1.87) | |||||
| *1/*2, *2/*17, *1/*35, *2/*13, *1/*3, *17/*35 | Intermediate metabolizer | 1197 (19.8) | |||||
| CYP2D6 | Atomoxetine, Codeine, Ondansetron, Tropisetron, Tamoxifen, Antidepressants | 355, 145 | *4/*4, *4/*68 + *4, *68 + *4/*68 + *4, *4/*5, *5/*68 + *4 | Poor metabolizer | 114 (1.89) | 2038 (33.71) | 982 (39.22) |
| *1/*2×2, *2/*2×2, *2×2/*41, *1×2/*2, *1/*1×2, *1×2/*41, *1×2/*1×2, *2×2/*2×2, *1×2/*2×2, *17/*2×2, *2×2/*35, *2×2/*27×2, *2×2/*33, *1×2/*17 | Ultrarapid metabolizer | 517 (8.55) | |||||
| *1/*4, *1/*68 + *4, *41/*41, *2/*4, *1/*5, *4/*41, *2/*68 + *4, *41/*68 + *4, *10/*41, *2/*5, *17/*41, *41/*5, *17/*4, *4/*10, *35/*4, *1/*3, *10/*68 + *4, *1/*13, *17/*68 + *4, *10/*10, *1/*40, *1/*6, *5/*10, *10/*17, *1/*8, *29/*4, *1/*36 + *10, *1/*7, *1_*2_*68, *17/*17, *17/*29, *41/*9, *9/*68 + *4 | Intermediate metabolizer | 1407 (23.28) | |||||
| CYP3A5 | Tacrolimus | 25, 9 | *1/*1 | Extensive metabolizer (CYP3A5 expressor) | 86 (1.42) | 1082 (17.9) | 1191 (47.56) |
| *1/*3, *1/*6, *1/*7 | Intermediate metabolizer (CYP3A5 expressor) | 996 (16.48) | |||||
| DPYD | Fluoropyrimidines | Intermediate metabolizer | 9 (0.15) | 9 (0.15) | 10 (0.4) | ||
| HLA-A | Carbamazepine | HLA-A*31:01 Hom | Risk of SJS/TEN | 10 (0.16) | 333 (5.43) | 125 (4.99) | |
| HLA-A*31:01 Het | 323 (5.27) | ||||||
| HLA-B | Phenytoin, Carbamazepine, Oxcarbazepine | (HLA-B*15:02 Hom) | Risk of SJS/TEN | 0 (0) | 25 (0.41) | 88 (3.51) | |
| HLA-B*15:02 Het | 25 (0.41) | ||||||
| HLA-B | Abacavir | (HLA-B*57:01 Hom) | Hypersensitivity risk | 2 (0.03) | 161 (2.62) | 151 (6.03) | |
| HLA-B*57:01 Het | 159 (2.59) | ||||||
| HLA-B | Allopurinol | (HLA-B*58:01 Hom) | Risk of SCAR | 4 (0.07) | 363 (5.92) | 165 (6.59) | |
| HLA-B*58:01 Het | 359 (5.85) | ||||||
| IFNL3 | Pegylated Interferon alpha, Ribavirin | 1 | rs12979860 Hom Alt | Unfavourable response | 626 (10.35) | 3175 (52.51) | 1353 (54.03) |
| rs12979860 Het | Unfavourable response | 2549 (42.15) | |||||
| NUDT15 | Thiopurines | 19, 20 | *1/*3 | Intermediate metabolizer | 245 (4.05) | 252 (4.17) | 185 (7.39) |
| *3/*3 | Poor metabolizer | 5 (0.08) | |||||
| Indeterminate | 2 (0.03) | ||||||
| RYR1 | Potent Volatile Anesthetic Agents, Succinylcholine | 2 | (rs111888148 c.1589 G > A, rs193922762 c.982 C > T) | Malignant Hyperthermia Susceptibility | 2 (0.03) | 2 (0.03) | 0 |
| SLCO1B1 | Simvastatin | 29, 36 | *1/*15, *1/*5, *1/*17, *1/*31 | Decreased function (Increased risk of myopathy) | 1616 (26.73) | 1957 (32.37) | 376 (15.02) |
| *15/*15, *5/*15, *15/*17, *5/*17, *5/*5, *17/*17 | Poor function (High risk of myopathy) | 341 (5.64) | |||||
| TPMT | Thiopurines | 43, 44 | *1/*3, *1/*2 | Intermediate metabolizer | 120 (1.98) | 121 (2.0) | 194 (7.75) |
| Poor metabolizer | 1 (0.02) | ||||||
| VKORC1 | Warfarin | 1 | rs9923231 (−1639G > A) Hom (AA) | Lower dosage requirement | 1596 (26.39) | 4395 (72.68) | 1230 (49.12) |
| rs9923231 (−1639G > A) Het (GA) | Lower dosage requirement | 2799 (46.29) |
NSAIDs Nonsteroidal anti-inflammatory drugs, SJS/TEN Stevens–Johnson syndrome, toxic epidermal necrolysis, SCAR Severe cutaneous adverse reaction.
Comparison of the frequencies of actionable genotypes/diplotypes in the Qatari population (6045 genomes) with that of the thousand genome populations (2,504 genomes). Examples of drugs predicted to have an effect based on CPIC guidelines are also provided.