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CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations

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Heyderman, Robert, Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200, Carr, Daniel F., Chaponda, Mas, Cornejo Castro, Elena M., Jorgensen, Andrea L., Khoo, Saye, Van Oosterhout, Joep J., Dandara, Collet, Kampira, Elizabeth, Ssali, Francis, Munderi, Paula and Pirmohamed, Munir (2014) 'CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations'. Journal of Antimicrobial Chemotherapy, Vol 69, Issue 12, pp. 3329-3334.

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Abstract

BACKGROUND:

Nevirapine, an NNRTI used in HIV treatment, can cause hypersensitivity reactions in 6%-10% of patients. In the most serious cases (1.3%) this can manifest as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

METHODS:

DNA samples were obtained and analysed from a total of 209 adult patients with nevirapine hypersensitivity (57 from a prospective cohort and 152 routine clinic patients) and compared with 463 control patients on nevirapine without any hypersensitivity. The case group included 70 patients with SJS/TEN. All individuals were genotyped for two SNPs in the CYP2B6 gene [c.516G>T (CYP2B6*9) and c.983T>C (CYP2B6*18)] using the TaqMan real-time genotyping platform. The replication cohort comprised 29 controls and 55 nevirapine hypersensitive patients, including 8 SJS/TEN cases.

RESULTS:

An association between the CYP2B6 c.983T>C polymorphism and nevirapine-induced SJS/TEN was observed. In the SJS/TEN group, 30% of individuals possessed at least one c.983T>C versus 16% in the tolerant group [P = 0.006; OR (95% CI) 2.24 (1.27-3.94)]. This association was not significant in the replication cohort [P = 0.075; OR (95% CI) 4.33 (0.80-23.57)]. Combined analysis resulted in an OR of 2.52 (95% CI 1.48-4.20; P = 0.0005) for the association of c.983T>C with SJS/TEN. No association was observed for c.983T>C with other hypersensitivity phenotypes and for CYP2B6 c.516G>T with any hypersensitivity phenotypes.

CONCLUSIONS:

Our data show an association between the c.983T>C polymorphism and nevirapine-induced SJS/TEN. CYP2B6 c.983T>C has a frequency of 5%-10% in a variety of African populations, but is not observed in Caucasians, thus representing an ethnic-specific predisposing factor.

Item Type: Article
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.5 DNA.
QV Pharmacology > QV 56 Adverse effects (General)
QV Pharmacology > QV 38 Drug action.
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1093/jac/dku315
Depositing User: Annmarie Hand
Date Deposited: 20 Nov 2014 15:26
Last Modified: 06 Feb 2018 13:07
URI: http://archive.lstmed.ac.uk/id/eprint/4549

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