Pharmacogenetics of Drug Hypersensitivity

Overview

Journal Pharmacogenomics

Specialties Genetics
Pharmacology

Date 2010 Jul 7

PMID 20602616

Citations 38

Authors

Elizabeth J Phillips

Simon A Mallal

Affiliations

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Abstract

Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world.

Citing Articles

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References

Zucman D, De Truchis P, Majerholc C, Stegman S, Caillat-Zucman S . Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007; 45(1):1-3. DOI: 10.1097/QAI.0b013e318046ea31. View

Likanonsakul S, Rattanatham T, Feangvad S, Uttayamakul S, Prasithsirikul W, Tunthanathip P . HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai patients. AIDS Res Ther. 2009; 6:22. PMC: 2774340. DOI: 10.1186/1742-6405-6-22. View

Daly A, Donaldson P, Bhatnagar P, Shen Y, Peer I, Floratos A . HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009; 41(7):816-9. DOI: 10.1038/ng.379. View

Komura K, Hasegawa M, Hamaguchi Y, Yukami T, Nagai M, Yachie A . Drug-induced hypersensitivity syndrome associated with human herpesvirus 6 and cytomegalovirus reactivation. J Dermatol. 2006; 32(12):976-81. DOI: 10.1111/j.1346-8138.2005.tb00885.x. View

Peyrieere H, Nicolas J, Siffert M, Demoly P, Hillaire-Buys D, Reynes J . Hypersensitivity related to abacavir in two members of a family. Ann Pharmacother. 2001; 35(10):1291-2. DOI: 10.1345/aph.1A022. View

Martin A, Nolan D, James I, Cameron P, Keller J, Moore C . Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS. 2005; 19(1):97-9. DOI: 10.1097/00002030-200501030-00014. View

Hammer S, Eron Jr J, Reiss P, Schooley R, Thompson M, Walmsley S . Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA. 2008; 300(5):555-70. DOI: 10.1001/jama.300.5.555. View

Hautekeete M, Horsmans Y, Van Waeyenberge C, Demanet C, Henrion J, Verbist L . HLA association of amoxicillin-clavulanate--induced hepatitis. Gastroenterology. 1999; 117(5):1181-6. DOI: 10.1016/s0016-5085(99)70404-x. View

DeJesus E, Herrera G, Teofilo E, Gerstoft J, Buendia C, Brand J . Abacavir versus zidovudine combined with lamivudine and efavirenz, for the treatment of antiretroviral-naive HIV-infected adults. Clin Infect Dis. 2004; 39(7):1038-46. DOI: 10.1086/424009. View

10.

Aberg J, Kaplan J, Libman H, Emmanuel P, Anderson J, Stone V . Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2009; 49(5):651-81. DOI: 10.1086/605292. View

11.

Colombo S, Rauch A, Rotger M, Fellay J, Martinez R, Fux C . The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir. J Infect Dis. 2008; 198(6):864-7. DOI: 10.1086/591184. View

12.

Trachtenberg E, Bhattacharya T, Ladner M, Phair J, Erlich H, Wolinsky S . The HLA-B/-C haplotype block contains major determinants for host control of HIV. Genes Immun. 2009; 10(8):673-7. PMC: 2873233. DOI: 10.1038/gene.2009.58. View

13.

Bossi P, Roujeau J, Bricaire F, Caumes E . Stevens-Johnson syndrome associated with abacavir therapy. Clin Infect Dis. 2002; 35(7):902. DOI: 10.1086/342571. View

14.

Quiralte J, Sanchez-Garcia F, Torres M, Blanco C, Castillo R, Ortega N . Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1999; 103(4):685-9. DOI: 10.1016/s0091-6749(99)70243-5. View

15.

Hung S, Chung W, Liou L, Chu C, Lin M, Huang H . 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(11):4134-9. PMC: 554812. DOI: 10.1073/pnas.0409500102. View

16.

Pellicano R, Ciavarella G, Lomuto M, Di Giorgio G . Genetic susceptibility to fixed drug eruption: evidence for a link with HLA-B22. J Am Acad Dermatol. 1994; 30(1):52-4. DOI: 10.1016/s0190-9622(94)70007-9. View

17.

Waters L, Mandalia S, Gazzard B, Nelson M . Prospective HLA-B*5701 screening and abacavir hypersensitivity: a single centre experience. AIDS. 2007; 21(18):2533-4. DOI: 10.1097/QAD.0b013e328273bc07. View

18.

Knowles S, SHAPIRO L, Shear N . Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Saf. 1999; 21(6):489-501. DOI: 10.2165/00002018-199921060-00005. View

19.

Park B, Naisbitt D, Gordon S, Kitteringham N, Pirmohamed M . Metabolic activation in drug allergies. Toxicology. 2001; 158(1-2):11-23. DOI: 10.1016/s0300-483x(00)00397-8. View

20.

Shiohara T, Inaoka M, Kano Y . Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int. 2006; 55(1):1-8. DOI: 10.2332/allergolint.55.1. View