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墨西哥人群中免疫相关基因单核苷酸多态性与登革出血热发病的关联

Association of Single-Nucleotide Polymorphisms in Immune-Related Genes with Development of Dengue Hemorrhagic Fever in a Mexican Population.

作者信息

Vargas-Castillo Angélica Berenice, Ruiz-Tovar Karina, Vivanco-Cid Héctor, Quiroz-Cruz Sarai, Escobar-Gutiérrez Alejandro, Cerna-Cortes Jorge Francisco, Vaughan Gilberto, Fonseca-Coronado Salvador

机构信息

1 Laboratorio de Microbiología Molecular, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional , Ciudad de México, México .

2 Laboratorio de Inmunobiología de Enfermedades Infecciosas, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México , Cuautitlán Izcalli, México .

出版信息

Viral Immunol. 2018 Apr;31(3):249-255. doi: 10.1089/vim.2017.0069. Epub 2017 Nov 13.

Abstract

Single-nucleotide polymorphisms (SNPs) occurring in immune-related genes have been associated with risk or protection for development of dengue, depending on ethnicity. Here, we genotyped seven SNPs located in immune response-related genes to identify their association with severe forms of dengue in patients from an endemic region in Mexico. One hundred and thirty-eight patients with dengue fever (DF), thirty-one dengue hemorrhagic fever (DHF) patients, as well as 304 healthy donors were genotyped by using a TaqMan-based approach. SNP analysis, including rs1800629 (TNF), rs4804803 (CD209), rs2780831 (JAK1), rs1801274 (FCGR2A), rs231775 (CTLA4), rs12979860, and rs8099917 (IFNL3), was performed. The rs1800629 A-allele in the TNF gene was associated with an increased risk of DHF (OR = 3.4, CI = 1.235-9.284 p = 0.0212) whereas SNPs rs4804803, rs2780831, rs1801274, rs231775, rs12979860, and rs8099917 showed no association in this cohort. These results show that allelic variations in TNF can play an important role in the development of DHF. However, the lack of association between all remaining SNPs and DHF suggests that the genetic background might directly modify the role of these immune-related molecules, leading to the milder illness often observed in a Mexican population.

摘要

免疫相关基因中出现的单核苷酸多态性(SNP)与登革热发病的风险或易感性相关,这取决于种族。在此,我们对位于免疫反应相关基因中的7个SNP进行基因分型,以确定它们与墨西哥一个流行地区患者严重登革热形式的关联。采用基于TaqMan的方法对138例登革热(DF)患者、31例登革出血热(DHF)患者以及304名健康供体进行基因分型。进行了SNP分析,包括rs1800629(TNF)、rs4804803(CD209)、rs2780831(JAK1)、rs1801274(FCGR2A)、rs231775(CTLA4)、rs12979860和rs8099917(IFNL3)。TNF基因中的rs1800629 A等位基因与DHF风险增加相关(OR = 3.4,CI = 1.235 - 9.284,p = 0.0212),而SNP rs4804803、rs2780831、rs1801274、rs231775、rs12979860和rs8099917在该队列中未显示出关联。这些结果表明,TNF中的等位基因变异可能在DHF的发生中起重要作用。然而,所有其余SNP与DHF之间缺乏关联表明,遗传背景可能直接改变这些免疫相关分子的作用,导致在墨西哥人群中经常观察到的病情较轻。

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