Drug

Gene target

ADR

Odds ratio

carbamazepine

HLA-B*1502

Stevens-Johnson syndrome (Asian)

OR=1023 1

Allopurinol

HLA-B*5801

Stevens-Johnson syndrome

OR=580 2

 

 

 

 

Azathioprine

6-MP

TMPT

Neutropenia

OR=49 3

Abacavir

HLA-B*5701

hypersensitivity

OR=33 4

Flucloxacillin

HLA-B*5701

Cholestatic hepatitis

OR=80 5

Irinotecan

(high doses)

UGT1A1*28

Severe neutropenia

OR=28 to 8 6,7

Nevirapine

HLA-DRB1*0101

hypersensitivity

OR=18 8

Simvastatin

SLC01B1*5

Myopathy

OR=17 9

Nevirapine

HLA Cw8-B14

hypersensitivity

OR=15 10

Warfarin

VKORC1+CYP2C9

Oral anticoagulant overdose

OR=10 11

Cisplatine

TPMT+COMT

Hearing loss

OR=17 12

Methotrexate

SLC01B1

Gastro intestinal toxicity

OR=16 13

NSAID

GSTM1 +GSTT1

Cytolytic hepatitis

OR=9 14

Diclofenac

UGT2B7*2

Hepatotoxicity

OR=8 15

Diclofenac

ABCC2 C-24T

Hepatotoxicity

OR=5 15

Izoniazid

NAT2

Cytolytic hepatitis

OR=4-5 16 ,17

Ximelagatran

HLA-DRB1*0701

Cytolytic hepatitis

OR=4 18

Tacrine

GSTM1 +GSTT1

Cytolytic hepatitis

OR=3 19

1. Chung W, Hung S, Hong H, Hsih M, Yang L, Ho H, Wu J, Chen Y. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486.

2. Hung S, Chung W, Liou L, Chu C, Lin M, Huang H, Lin Y, Lan J, Yang L, Hong H, Chen M, Lai P, Wu M, Chu C, Wang K, Chen C, Fann C, Wu J, Chen Y. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005;102:4134-4139.

3. Nelson M, Bacanu S-A, Mosteller M, Li L, Bowman C, Roses AD, Lai E, Ehm M. Genome-wide approaches to identify pharmacogenetic contributions to adverse drug reactions. Pharmacogenomics J. 2008:Epub ahead of print.

4. Mallal S, Phillips E, Carosi G, Molina J, Workman C, Tomazic J, Jägel-Guedes E, Rugina S, Kozyrev O, Cid J, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358:568-579.

5. Daly A, Donaldson P, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly M, Goldstein D, John S, Nelson M, Graham J, Park B, Dillon J, Bernal W, Cordell H, Pirmohamed M, Aithal G, Day C, Consortium. DSIS. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009;41:816-819.

6. Hoskins J, Goldberg R, Qu P, Ibrahim J, McLeod H. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst 2007;99:1290-1295.

7. Côté J, Kirzin S, Kramar A, Mosnier J, Diebold M, Soubeyran I, Thirouard A, Selves J, Laurent-Puig P, Ychou M. UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. J Clin Oncol 2007;13:3269-3275.

8. Martin A, Nolan D, James I, Cameron P, Keller J, Moore C, Phillips E, Christiansen F, Mallal S. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 2005;19:97-99.

9. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med 2008;359:789-799.

10. Littera R, Carcassi C, Masala A, Piano P, Serra P, Ortu F, Corso N, Casula B, La Nasa G, Contu L, Manconi P. HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS 2006;20:1624-1626.

11. Quteineh L, Verstuyft C, Descot C, Dubert L, Robert A, Jaillon P, Becquemont L. Vitamin K epoxide reductase (VKORC1) genetic polymorphism is associated to oral anticoagulant overdose. Thromb Haemost 2005;94:690-1.

12. Ross CJ, Katzov-Eckert H, Dube MP, Brooks B, Rassekh SR, Barhdadi A, Feroz-Zada Y, Visscher H, Brown AM, Rieder MJ, Rogers PC, Phillips MS, Carleton BC, Hayden MR. Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy. Nat Genet 2009;41:1345-9.

13. Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, Chan D, Sparreboom A, Giacomini KM, Pui CH, Evans WE, Relling MV. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 2009;27:5972-8.

14. Lucena M, Andrade R, Martínez C, Ulzurrun E, García-Martín E, Borraz Y, Fernández M, Romero-Gomez M, Castiella A, Planas R, Costa J, Anzola S, Agúndez J. Glutathione S-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury. Hepatology 2009;48:588-596.

15. Daly A, Aithal G, Leathart J, Swainsbury R, Dang T, Day C. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. gastroenterology 2007;132:272-81.

16. Huang YS, Chern H, Su WJ, Wu JC, Lai SL, Yang SY, Chang FY, Lee SD. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology 2002;35:883-889.

17. Possuelo L, Castelan J, de Brito T, Ribeiro A, Cafrune P, Picon P, Santos A, Teixeira R, Gregianini T, Hutz M, Rossetti M, Zaha A. Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil. Eur J Clin Pharmacol 2008;64:673-681.

18. Kindmark A, Jawaid A, Harbron C, Barratt B, Bengtsson O, Andersson T, Carlsson S, Cederbrant K, Gibson N, Armstrong M, Lagerström-Fermér M, Dellsén A, Brown E, Thornton M, Dukes C, Jenkins S, Firth M, Harrod G, Pinel T, Billing-Clason S, Cardon L, March R. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J. 2008;8:186-195.

19. Simon T, Becquemont L, Mary-Krause M, de Waziers I, Beaune P, Funck-Brentano C, Jaillon P. Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther 2000;67:432-7.