Angulo Jenniffer, Pino Karla, Echeverría-Chagas Natalia, Marco Claudia, Martínez-Valdebenito Constanza, Galeno Héctor, Villagra Eliecer, Vera Lilian, Lagos Natalia, Becerra Natalia, Mora Judith, Bermúdez Andrea, Cárcamo Marcela, Díaz Janepsy, Miquel Juan Francisco, Ferrés Marcela, López-Lastra Marcelo
Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia.
Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Clin Infect Dis. 2015 Dec 15;61(12):e62-9. doi: 10.1093/cid/civ830. Epub 2015 Sep 22.
Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α).
A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629.
Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF -308G>A).
The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis.
安第斯病毒(ANDV)是智利汉坦病毒心肺综合征(HCPS)的唯一病原体,病死率约为35%。影响ANDV感染结果的个体宿主因素尚不清楚。在这项病例对照基因关联分析中,我们探究了单核苷酸多态性(SNP)rs12979860、rs8099917和rs1800629与ANDV所致疾病临床结局之间的联系。已知SNP rs12979860和rs8099917在白细胞介素28B基因(IL28B)的差异表达中起作用,而SNP rs1800629与肿瘤坏死因子α基因(TNF-α)的表达有关。
对2006年至2014年间收集的238份确诊ANDV感染患者的样本进行基因分型,检测SNP rs12979860、rs8099917和rs1800629,并根据疾病严重程度进行分类。
对IL28B的SNP rs12979860和rs8099917的分析显示,次要等位基因的纯合性(分别为TT和GG)与疾病进展较轻有关,而IL28B两个SNP中主要等位基因的杂合性或纯合性(分别为CT/CC和TG/TT)与严重疾病有关。未观察到TNF-α的SNP rs1800629(TNF -308G>A)与HCPS临床结局有关联。
IL28B的SNP rs12979860和rs8099917而非TNF-α的SNP rs1800629与ANDV所致疾病的临床结局有关,提示IL28B表达与ANDV发病机制之间可能存在联系。