A multivariate genetic analysis confirms rs5010528 in the human leucocyte antigen-C locus as a significant contributor to Stevens-Johnson syndrome/toxic epidermal necrolysis susceptibility in a Mozambique HIV population treated with nevirapine

The Journal of Antimicrobial Chemotherapy
Cinzia CiccacciPaola Borgiani

Abstract

Nevirapine is used in developing countries for the treatment of HIV infection, but its use is associated with rare serious adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, an association between rs5010528 in the human leucocyte antigen (HLA)-C locus and SJS/TEN susceptibility has been described in sub-Saharan populations. Our aim was to verify this association in a population of nevirapine-treated patients from Mozambique. The rs5010528 SNP was analysed by direct sequencing in 27 patients who had developed SJS/TEN and 75 patients who did not develop adverse reactions after nevirapine treatment. A case-control association study was conducted. A multivariate analysis was performed in order to evaluate the role of HLA-C also in relation to other susceptibility genetic factors (CYP2B6, TRAF3IP2, HCP5, PSORS1C1 and GSTM1 genes). rs5010528 was significantly associated with a higher risk of developing SJS/TEN; the variant allele was more frequent in cases than in controls, conferring a high risk of developing this adverse reaction in carriers (OR = 5.72 and P = 0.0002 at genotype level, OR = 3.51 and P = 0.0002 at allelic level). The multivariate analysis showed that the HLA-C SN...Continue Reading

References

Oct 18, 2003·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jerry O SternDouglas L Mayers
Oct 23, 2009·AIDS Research and Therapy·Sirirat LikanonsakulTatsuo Shioda
Sep 10, 2011·AIDS Research and Human Retroviruses·Shicheng GaoBo Dong
Jun 19, 2013·European Journal of Clinical Pharmacology·Cinzia CiccacciGiuseppe Liotta

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Citations

Sep 14, 2021·Annual Review of Pharmacology and Toxicology·Kanoot JaruthamsophonMunir Pirmohamed

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