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首页> 外文期刊>Clinical and Translational Allergy >CYP2B6*18 is associated with nevirpine hypersensitivity independently of HLA-C*04:01 in a Malawian HIV population
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CYP2B6*18 is associated with nevirpine hypersensitivity independently of HLA-C*04:01 in a Malawian HIV population

机译：CYP2B6 * 18与马拉维HIV人群中的独立于HLA-C * 04：01的奈韦平超敏反应相关

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Nevirapine (NVP), a non-nucleoside reverse transcriptaseinhibitor (NNRTI) used in human immunodeficiencyvirus (HIV) treatment can cause hypersensitivity reactionsin 6-10% of patients, which in the most serious cases(1.3%) can manifest as Stevens-Johnson Syndrome (SJS)or Toxic Epidermal Necrolysis (TEN). A total of 209patients with NVP hypersensitivity (57 from a prospectivecohort and 152 clinic patients) were compared with 463control patients on NVP without any hypersensitivity.The case group included 70 patients with serious blisteringreactions (SJS or TEN). All individuals were genotyped for2 SNPs in the CYP2B6 gene (c.516G>T [CYP2B6*9] andc.983T>C [CYP2B6*18]) using the TaqMan real-time genotypingplatform. A replication cohort of 29 controls and31 nevirapine hypersensitive patients, including 8 SJS/TENcases, was subsequently typed. An association between theCYP2B6*18 polymorphism and NVP-induced SJS/TENwas observed (p=0.013). In the SJS/TEN group, 30% ofindividuals possessed at least one *18 allele vs. 16% in thetolerant group (p=0.006; OR (95% CI) 2.24(1.27-3.94)).This association was also borderline significant in thereplication cohort (p=0.075). Combined analysis resultedin an odds ratio of 2.52 (95% CI 1.48-4.20; p=0.0005) forthe association of SJS/TEN with CYP2B6*18. Thisassociation was not observed for other hypersensitivityphenotypes. Data show a putative association between theCYP2B6*18 polymorphism and nevirapine-induced SJS/TEN. CYP2B6*18 has a frequency of around 5-10% inAfrican populations but is not observed in Caucasians,and this may therefore represent an ethnicity-specificpredisposing factor.
机译：奈韦拉平（NVP）是一种用于人类免疫缺陷病毒（HIV）治疗的非核苷类逆转录酶抑制剂（NNRTI），可在6-10％的患者中引起超敏反应，在最严重的情况下（1.3％）可表现为史蒂文斯-约翰逊综合症（SJS）或毒性表皮坏死症（TEN）。比较了209例NVP超敏反应患者（前瞻性队列中的57例患者和152例临床患者）与463例无任何超敏反应的NVP对照患者。病例组包括70例严重水疱反应（SJS或TEN）。使用TaqMan实时基因分型平台对CYP2B6基因中的2个SNP进行基因分型（c.516G> T [CYP2B6 * 9]和c.983T> C [CYP2B6 * 18]）。随后输入了29例对照和31例奈韦拉平高敏感性患者的复制队列，其中包括8例SJS / TEN病例。观察到CYP2B6 * 18多态性和NVP诱导的SJS / TEN之间的关联（p = 0.013）。在SJS / TEN组中，30％的个体拥有至少一个* 18等位基因，而在耐受组中则为16％（p = 0.006; OR（95％CI）2.24（1.27-3.94））。重复队列（p = 0.075）。组合分析得出SJS / TEN与CYP2B6 * 18关联的比值比为2.52（95％CI 1.48-4.20; p = 0.0005）。对于其他超敏性表型未观察到这种关联。数据显示CYP2B6 * 18多态性与奈韦拉平诱导的SJS / TEN之间存在推测的关联。 CYP2B6 * 18在非洲人群中的发病率约为5-10％，但在高加索人中没有观察到，因此这可能代表特定种族的诱因。

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