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CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2014 Dec; Vol. 69 (12), pp. 3329-34. Date of Electronic Publication: 2014 Aug 20. - Publication Year :
- 2014
-
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).<br />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.<br />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.<br />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.<br /> (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
- Subjects :
- Adult
Anti-HIV Agents therapeutic use
Case-Control Studies
Cohort Studies
Female
Genotype
Genotyping Techniques
HIV Infections drug therapy
Humans
Malawi
Male
Middle Aged
Nevirapine therapeutic use
Prospective Studies
Uganda
Anti-HIV Agents adverse effects
Cytochrome P-450 CYP2B6 genetics
Drug Hypersensitivity genetics
Nevirapine adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 69
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 25147095
- Full Text :
- https://doi.org/10.1093/jac/dku315