Table 1 Basic characteristics of the selected VIP variants from the PharmGKB database and genotype frequencies in the Wa population

rs11572325

1

59896030

intron_variant

CYP2J2

T/A

0.043

0

17

183

rs10889160

1

59896449

intron_variant

CYP2J2

C/T

0.108

0

43

157

rs1760217

1

97137438

genic_downstream_transcript_variant,intron_variant

Genotypes AA + AG are associated with decreased survival when treated with antineoplastic agents in people with Pancreatic Neoplasms as compared to genotype GG.

antineoplastic agents

Efficacy

DPYD

3

G/A

0.330

24

84

92

rs1801159

1

97515839

coding_sequence_variant,genic_downstream_transcript_variant,intron_variant,missense_variant

Genotype TT is not associated with increased risk of Neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotypes CC + CT.

capecitabine/fluorouracil

Toxicity

DPYD

1A

C/T

0.265

10

85

103

rs1801265

1

97883329

non_coding_transcript_variant,intron_variant,coding_sequence_variant,5_prime_UTR_variant,missense_variant

Genotypes AA + AG is associated with decreased Drug Toxicity when treated with capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype GG.

fluorouracil/capecitabine

Toxicity

DPYD

1A

G/A

0.095

1

36

163

rs5275

1

186673926

3_prime_UTR_variant

Genotype AA is associated with increased progression-free survival and overall survival when treated with capecitabine and oxaliplatin in people with Colorectal Neoplasms as compared to genotypes AG + GG.

capecitabine oxaliplatin

Efficacy

PTGS2

3

G/A

0.175

3

64

133

rs20417

1

186681189

upstream_transcript_variant,non_coding_transcript_variant

Allele C is not associated with response to cetuximab or panitumumab in people with Colorectal Neoplasms as compared to allele G.

aspirin/ibuprofen/rofecoxib

Efficacy

PTGS2

3

G/C

0.003

0

1

199

rs12139527

1

201040054

missense_variant,coding_sequence_variant,intron_variant

CACNA1S

G/A

0.040

0

16

184

rs3850625

1

201047168

coding_sequence_variant,missense_variant

CACNA1S

A/G

0.003

0

1

199

rs2306238

1

237550803

intron_variant

RYR2

A/G

0.223

9

71

120

rs2231142

4

88131171

coding_sequence_variant,missense_variant

Genotypes GT + TT are not associated with increased likelihood of statin-related myopathy when treated with atorvastatin or simvastatin as compared to genotype GG.

rosuvastatin/rosuvastatin

Efficacy/Metabolism/PK

ABCG2

2A

T/G

0.196

7

64

128

rs2231137

4

88139962

coding_sequence_variant,missense_variant

Genotypes CT + TT is not associated with increased risk of Neutropenia when treated with valganciclovir in people with Kidney Transplantation as compared to genotype CC.

dasatinib imatinib nilotinib/irinotecan/imatinib

Other/Toxicity/Dosage

ABCG2

3

C/T

0.538

55

103

40

rs698

4

99339632

coding_sequence_variant,non_coding_transcript_variant,missense_variant

Genotype CT is associated with decreased likelihood of complete response when treated with cisplatin and cyclophosphamide in women with Ovarian Neoplasms as compared to genotypes CC + TT.

cisplatin cyclophosphamide

Efficacy

ADH1C

3

C/T

0.108

9

25

166

rs776746

7

99672916

intron_variant,splice_acceptor_variant,genic_downstream_transcript_variant,downstream_transcript_variant

Genotype CC is associated with decreased dose of tacrolimus in people with Kidney Transplantation as compared to genotypes CT + TT.

tacrolimus

Metabolism/PK

CYP3A5

1A

T/C

0.150

29

2

169

rs2242480

7

99763843

intron_variant

CYP3A4 *1G/*1G is associated with decreased metabolism of fentanyl in human liver microsomes as compared to CYP3A4 *1/*1 + *1/*1G.

tacrolimus

Metabolism/PK

CYP3A4

1B

T/C

0.337

18

98

83

rs1805123

7

150948446

missense_variant,coding_sequence_variant,genic_downstream_transcript_variant

Allele G is associated with decreased QT interval as compared to genotype TT.

KCNH2

3

G/T

0.095

0

38

162

rs4646244

8

18390208

upstream_transcript_variant,genic_upstream_transcript_variant,intron_variant

Allele A is associated with increased risk of Hepatitis when treated with ethambutol, isoniazid, pyrazinamide and rifampin in people with Tuberculosis.

ethambutol isoniazid pyrazinamide rifampin

Toxicity/Metabolism/PK

NAT2

3

A/T

0.223

13

62

122

rs4271002

8

18390758

upstream_transcript_variant,genic_upstream_transcript_variant,intron_variant

Allele C is associated with increased risk of intolerance of aspirin in people with Asthma as compared to allele G.

aspirin

Toxicity

NAT2

3

C/G

0.241

9

77

111

rs1041983

8

18400285

coding_sequence_variant,synonymous_variant

NAT2 *6A/*7B is associated with increased likelihood of Toxic liver disease when treated with isoniazid and rifampin in people with Tuberculosis.

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

T/C

0.455

42

96

60

rs1801280

8

18400344

missense_variant,coding_sequence_variant

NAT2 *5A is associated with increased risk of severe cutaneous adverse reactions when treated with sulfamethoxazole and trimethoprim in people with Acquired Immunodeficiency Syndrome.

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

C/T

0.043

0

17

183

rs1799929

8

18400484

coding_sequence_variant,synonymous_variant

Allele T is not associated with increased risk of hepatotoxicity when treated with ethambutol, isoniazid, pyrazinamide and rifampin in people with Tuberculosis as compared to allele C.

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

T/C

0.043

0

17

183

rs1799930

8

18400593

missense_variant,coding_sequence_variant

NAT2 *6/*7 is associated with increased likelihood of Toxic liver disease when treated with ethambutol, isoniazid, pyrazinamide and rifampin in people with Tuberculosis

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

A/G

0.234

12

69

118

rs1208

8

18400806

missense_variant,coding_sequence_variant

NAT2 *5B/*7B + *6A/*6A + *6A/*7B + *7B/*7B are associated with increased risk of Toxic liver disease when treated with ethambutol, isoniazid, pyrazinamide and rifampin in people with Tuberculosis.

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

G/A

0.043

0

17

183

rs1799931

8

18400860

missense_variant,coding_sequence_variant

NAT2 *6/*7 is associated with increased likelihood of Toxic liver disease when treated with ethambutol, isoniazid, pyrazinamide and rifampin in people with Tuberculosis.

ethambutol isoniazid pyrazinamide rifampin

Toxicity

NAT2

1B

A/G

0.230

10

72

118

rs1495741

8

18415371

None

Genotype AA is associated with increased likelihood of Toxic liver disease when treated with Drugs For Treatment Of Tuberculosis as compared to genotypes AG + GG.

Drugs For Treatment Of Tuberculosis

Toxicity

NAT2

3

G/A

0.370

26

93

77

rs2115819

10

45405641

intron_variant

Genotype GG is associated with increased FEV1 response when treated with montelukast in people with Asthma as compared to genotypes AA + AG.

montelukast

Efficacy

ALOX5

3

A/G

0.140

9

38

153

rs4244285

10

94781859

coding_sequence_variant,synonymous_variant

Allele A is associated with decreased exposure to clopidogrel active metabolite when treated with clopidogrel in healthy individuals as compared to allele G.

nelfinavir

Metabolism/PK

CYP2C19

3

A/G

0.389

31

92

75

rs1057910

10

94981296

missense_variant,coding_sequence_variant

CYP2C9 *1/*3 is associated with decreased metabolism of meloxicam in healthy individuals as compared to CYP2C9 *1/*1.

piroxicam

Metabolism/PK

CYP2C9

1A

C/A

0.023

0

9

191

rs11572103

10

95058349

missense_variant,coding_sequence_variant

CYP2C8 *1/*3 + *3/*3 is associated with increased response to paclitaxel in women with Breast Neoplasms as compared to CYP2C8 *1/*1.

rosiglitazone

Toxicity

CYP2C8

3

A/T

0.010

0

4

196

rs7909236

10

95069673

upstream_transcript_variant

Allele T is not associated with concentrations of imatinib in people with Neoplasms as compared to allele G.

CYP2C8

T/G

0.030

0

12

188

rs17110453

10

95069772

upstream_transcript_variant

Genotypes AC + CC is not associated with resistance to clopidogrel in people with Stroke as compared to genotype AA.

CYP2C8

C/A

0.363

26

93

81

rs3813867

10

133526101

non_coding_transcript_variant,upstream_transcript_variant

CYP2E1 *1/*5B is associated with increased elimination rate of acetaminophen in people with Liver Diseases, Alcoholic as compared to CYP2E1 *1/*1.

Drugs For Treatment Of Tuberculosis

Toxicity

CYP2E1

3

C/G

0.075

3

24

172

rs2031920

10

133526341

non_coding_transcript_variant,upstream_transcript_variant

Genotypes CT + TT are associated with increased risk of Toxic liver disease when treated with Drugs For Treatment Of Tuberculosis in people with Tuberculosis as compared to genotype CC.

Drugs For Treatment Of Tuberculosis

CYP2E1

3

T/C

0.098

3

33

164

rs6413432

10

133535040

intron_variant

Genotype TT is associated with increased progression-free survival when treated with cisplatin and cyclophosphamide in women with Ovarian Neoplasms as compared to genotype AT.

cisplatin cyclophosphamide

Efficacy

CYP2E1

3

A/T

0.025

0

10

190

rs2070676

10

133537633

intron_variant

Genotype CG is associated with increased risk of severe emesis when treated with cisplatin and cyclophosphamide in women with Ovarian Neoplasms as compared to genotype CC.

cisplatin cyclophosphamide

Efficacy/Toxicity

CYP2E1

3

G/C

0.175

3

64

133

rs5219

11

17388025

missense_variant,stop_gained,5_prime_UTR_variant,intron_variant,coding_sequence_variant

Allele T is associated with decreased activity of KCNJ11 when treated with glibenclamide pancreatic islet cells.

gliclazide

Efficacy

KCNJ11

3

T/C

0.340

9

118

73

rs1801028

11

113412762

missense_variant,coding_sequence_variant

Genotypes CG + GG are not associated with response to antipsychotics in people with Schizophrenia as compared to genotype CC.

DRD2

C/G

0.005

0

2

198

rs2306283

12

21176804

missense_variant,coding_sequence_variant

Genotype AA is associated with decreased response to rocuronium as compared to genotypes AG + GG.

pitavastatin

Metabolism/PK

SLCO1B1

3

A/G

0.168

5

57

138

rs4516035

12

47906043

upstream_transcript_variant

Allele T is associated with increased jejunal CYP3A4 protein levels as compared to allele C.

midazolam

Metabolism/PK

VDR

3

C/T

0.025

0

10

190

rs762551

15

74749576

intron_variant

CYP1A2 *1K is associated with decreased transcription of CYP1A2 when exposed to xenobiotics in B1642 cells.

caffeine

Toxicity

CYP1A2

3

C/A

0.321

17

91

87

rs2472304

15

74751897

intron_variant

Allele A is associated with increased likelihood of remission when treated with paroxetine in people with Depressive Disorder, Major as compared to allele G.

paroxetine/erlotinib

Efficacy/Metabolism/PK

CYP1A2

3

A/G

0.083

0

33

167

rs750155

16

28609251

5_prime_UTR_variant,intron_variant,genic_upstream_transcript_variant,upstream_transcript_variant

Allele T is not associated with ABT-751 pharmacokinetic parameters when treated with ABT-751 in people with Neoplasms as compared to allele C.

SULT1A1

T/C

0.406

22

112

58

rs1800764

17

63473168

None

ACE

C/T

0.269

14

79

106

rs4291

17

63476833

upstream_transcript_variant

Genotypes AT + TT are associated with increased risk of aspirin intolerance when exposed to aspirin in people with Asthma as compared to genotype AA.

captopril/aspirin/amlodipine chlorthalidone lisinopril

Efficacy/Toxicity/Efficacy

ACE

3

T/A

0.500

0

200

0

rs4267385

17

63506395

None

Genotypes CC + CT are associated with same protective properties against angiotensin-converting enzyme inhibitors-induced cough when treated with Ace Inhibitors, Plain in people with homozygous GG genotype for rs4343 as compared to genotype TT.

Ace Inhibitors Plain

Toxicity

ACE

3

T/C

0.260

16

71

111

rs2108622

19

15879621

missense_variant,coding_sequence_variant

CYP4F2 *1/*3 + *3/*3 are associated with increased exposure to Vitamin K1 in healthy individuals as compared to CYP4F2 *1/*1.

warfarin

Dosage

CYP4F2

1A

T/C

0.173

6

57

137

rs3093105

19

15897578

missense_variant,coding_sequence_variant

Allele C is associated with increased catalytic activity of CYP4F2 when treated with vitamin e in Sf9 insect cells transfected with CYP4F2 as compared to allele A.

vitamin e

Metabolism/PK

CYP4F2

3

C/A

0.497

1

198

0

rs8192726

19

40848591

intron_variant

Genotypes AC + CC are associated with increased plasma concentration (p=0.028) of efavirenz in people with HIV Infections as compared to genotype AA.

efavirenz

Other

CYP2A6

4

A/C

0.163

8

49

143

rs1051298

21

45514912

intron_variant,3_prime_UTR_variant

Allele G is associated with increased progression-free survival when treated with bevacizumab and pemetrexed in people with Lung Neoplasms as compared to allele A.

pemetrexed

Efficacy

SLC19A1

3

G/A

0.431

8

152

35

rs1051296

21

45514947

intron_variant,3_prime_UTR_variant

SLC19A1

A/C

0.469

44

95

56

rs1131596

21

45538002

missense_variant,5_prime_UTR_variant,synonymous_variant,genic_upstream_transcript_variant,coding_sequence_variant

Allele G is not associated with response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele A.

SLC19A1

G/A

0.490

33

129

37

rs1065852

22

42130692

intron_variant,missense_variant,coding_sequence_variant

Allele A is associated with decreased clearance of alpha-hydroxymetoprolol in healthy individuals as compared to allele G.

paroxetine

Metabolism/PK

CYP2D6

1A

G/A

0.430

29

170

1