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. (11th May 2018)

• Record Type: Journal Article
• Authors: Ciccacci, Cinzia; Politi, Cristina; Mancinelli, Sandro; Ciccacci, Fausto; Lucaroni, Francesca; Novelli, Giuseppe; Marazzi, Maria Cristina; Palombi, Leonardo; Borgiani, Paola
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 8(2018)
• Page Start: 2137
• Page End: 2140
• Publication Date: 2018-05-11
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky180
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: 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. Methods: 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). Results: 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 SNP, CYP2B6 (rs28399499), TRAF3IP2 (rs76228616) and GSTM1 (null genotype) can explain 25% of the susceptibility to this reaction, with the HLA-C SNP as the most significant contributor ( P = 0.02 and OR = 5.64). Conclusions: Our study confirmed the association of the rs5010528 SNP in the HLA-C region with susceptibility to developing SJS/TEN in a population from Mozambique, suggesting that it could be a good genomic biomarker for SJS/TEN susceptibility in different sub-Saharan populations.