title: A pharmacogenetics study in Mozambican patients treated with nevirapine: full resequencing of TRAF3IP2 gene shows a novel association with SJS/TEN susceptibility.
abstract: Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33-10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19-16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN.
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Rome 00133, Italy. cinziaciccacci@libero.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Rome 00133, Italy. sara.rufini@hotmail.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Rufini
authors.affiliation: Department of Biomedicine and Prevention, Epidemiology Section, University of Rome "Tor Vergata", Rome 00133, Italy. sandro.mancinelli@uniroma2.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Mancinelli
authors.affiliation: Department of Biomedicine and Prevention, Epidemiology Section, University of Rome "Tor Vergata", Rome 00133, Italy. ersilia.buonomo@uniroma2.it.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Buonomo
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Rome 00133, Italy. emiliano.giardina@uniroma2.it.|Laboratory of Molecular Genetics UILDM, Fondazione Santa Lucia, Rome 00179, Italy. emiliano.giardina@uniroma2.it.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.affiliation: Department of Biomedicine and Prevention, Epidemiology Section, University of Rome "Tor Vergata", Rome 00133, Italy. paola.scarcella@uniroma2.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Scarcella
authors.affiliation: Department of Human Sciences, LUMSA University, Rome 00193, Italy. marazzi@lumsa.it.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Marazzi
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Rome 00133, Italy. novelli@med.uniroma2.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Department of Biomedicine and Prevention, Epidemiology Section, University of Rome "Tor Vergata", Rome 00133, Italy. leonardo.palombi@gmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Rome 00133, Italy. borgiani@med.uniroma2.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D009073:Mozambique; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D016017:Odds Ratio; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019380:Anti-HIV Agents; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019829:Nevirapine