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
Autor: | Paola Borgiani, Francesca Lucaroni, Cristina Politi, Giuseppe Novelli, Sandro Mancinelli, Cinzia Ciccacci, Fausto Ciccacci, Maria Cristina Marazzi, Leonardo Palombi |
---|---|
Rok vydání: | 2018 |
Předmět: |
Microbiology (medical)
Adult Nevirapine Genotype Anti-HIV Agents Settore MED/42 - Igiene Generale e Applicata Population HIV Infections HLA-C Antigens 030226 pharmacology & pharmacy Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Gene Frequency concentrations SNP Medicine Humans HIV Nevirapine efavirenz concentrations Pharmacology (medical) Genetic Predisposition to Disease 030212 general & internal medicine Allele education Adverse effect Alleles Mozambique Pharmacology education.field_of_study business.industry HCP5 HIV efavirenz medicine.disease Toxic epidermal necrolysis Infectious Diseases Case-Control Studies Stevens-Johnson Syndrome Immunology Multivariate Analysis Female business medicine.drug |
Zdroj: | The Journal of antimicrobial chemotherapy. 73(8) |
ISSN: | 1460-2091 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |