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HCP5基因变异(RS3099844)导致莫桑比克人群中奈韦拉平诱发的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症易感性。

HCP5 genetic variant (RS3099844) contributes to Nevirapine-induced Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis susceptibility in a population from Mozambique.

作者信息

Borgiani Paola, Di Fusco Davide, Erba Fulvio, Marazzi Maria C, Mancinelli Sandro, Novelli Giuseppe, Palombi Leonardo, Ciccacci Cinzia

机构信息

Department of Biomedicine and Prevention, School of Medicine, University of Rome "Tor Vergata", Rome, Italy,

出版信息

Eur J Clin Pharmacol. 2014 Mar;70(3):275-8. doi: 10.1007/s00228-013-1622-5. Epub 2013 Dec 10.

Abstract

PURPOSE

Nevirapine (NVP) is an anti-retroviral drug used for the treatment of HIV infection, that may cause several severe adverse events, including Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). A recent whole genome association study highlighted a strong association with allopurinol-induced SJS/TEN within the HCP5 and PSORS1C1 genes in the Japanese population. Our aim was to verify the contribution of these two genes in the susceptibility to NVP-induced SJS/TEN in a population from Mozambique.

METHODS

Genotyping of PSORS1C1 rs2233945 and HCP5 rs3099844 SNPs was performed in a sample of 27 patients with SJS/TEN and 76 controls. A case-control and a haplotype analysis were performed.

RESULTS

The HCP5 rs3099844 variant allele was significantly associated with the SJS/TEN susceptibility (OR = 2.03 and P = 0.039). The TA haplotype, carrying both the variant alleles of the two genes, showed a higher risk for developing SJS/TEN (OR = 3.44and P = 0.003). The regression analysis confirmed the contribution of HCP5 rs3099844 SNP (OR = 2.05, P = 0.047). By a log-linear model, we also investigated for interaction between HCP5 rs309844 and PSORS1C1 rs2233945 SNPs with respect to SJS/TEN risk, and we observed a strong interaction between the two SNPs (P = 0.005).

CONCLUSIONS

We confirmed the association of HCP5 with the SJS/TEN susceptibility in a population from Mozambique treated with NVP.

摘要

目的

奈韦拉平(NVP)是一种用于治疗HIV感染的抗逆转录病毒药物,可能会引起多种严重不良事件,包括史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)。最近一项全基因组关联研究强调,在日本人群中,HCP5和PSORS1C1基因与别嘌醇诱导的SJS/TEN密切相关。我们的目的是验证这两个基因对莫桑比克人群中NVP诱导的SJS/TEN易感性的影响。

方法

对27例SJS/TEN患者和76例对照样本进行PSORS1C1 rs2233945和HCP5 rs3099844单核苷酸多态性(SNP)基因分型。进行病例对照分析和单倍型分析。

结果

HCP5 rs3099844变异等位基因与SJS/TEN易感性显著相关(比值比[OR]=2.03,P=0.039)。携带两个基因变异等位基因的TA单倍型显示发生SJS/TEN的风险更高(OR=3.44,P=0.003)。回归分析证实了HCP5 rs3099844 SNP的作用(OR=2.05,P=0.047)。通过对数线性模型,我们还研究了HCP5 rs309844和PSORS1C1 rs2233945 SNPs之间关于SJS/TEN风险的相互作用,我们观察到这两个SNP之间存在强烈的相互作用(P=0.005)。

结论

我们证实在接受NVP治疗的莫桑比克人群中,HCP5与SJS/TEN易感性相关。

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