A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility

International Journal of Molecular Sciences

Cinzia Ciccacci³  Sara Rufini³  Sandro Mancinelli¹  Ersilia Buonomo¹  Emiliano Giardina³  Paola Scarcella¹  Maria C. Marazzi²  Giuseppe Novelli³  Leonardo Palombi¹  Paola Borgiani³ 

[1] Department of Biomedicine and Prevention, Epidemiology Section, University of Rome “Tor Vergata”, Rome 00133, Italy; E-Mails:;Department of Human Sciences, LUMSA University, Rome 00193, Italy; E-Mail:;Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, Rome 00133, Italy; E-Mails:

关键词: pharmacogenetics;    polymorphisms;    Steven–Johnson Syndrome (SJS);    Toxic Epidermal Necrolysis (TEN);    TRAF3IP2 gene;   

DOI  :  10.3390/ijms16035830

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.