Table 1 Actionable genotype/diplotype frequencies of clinically important pharmacogenes in the Qatari population.

From: A population study of clinically actionable genetic variation affecting drug response from the Middle East

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)

  1. NSAIDs Nonsteroidal anti-inflammatory drugs, SJS/TEN Stevens–Johnson syndrome, toxic epidermal necrolysis, SCAR Severe cutaneous adverse reaction.
  2. 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.
Back to article page