Sánchez-Leyva Marina, Sánchez-Zazueta Jorge Guillermo, Osuna-Ramos Juan Fidel, Rendón-Aguilar Horacio, Félix-Espinoza Rafael, Becerra-Loaiza Denisse Stephania, Sánchez-García Dulce Carolina, Romero-Quintana José Geovanni, Castillo Ureta Hipolito, Velarde-Rodríguez Ismael, Velarde-Félix Jesús Salvador
1 Departamento de Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, México .
2 Cuerpo Académico Inmunogenética y Evolución UAS-CA-265, Unidad Académica Escuela de Biología, Universidad Autónoma de Sinaloa , Culiacán, México .
Viral Immunol. 2017 Oct;30(8):615-621. doi: 10.1089/vim.2017.0029. Epub 2017 Jun 26.
To evaluate the association of the -308 and -238 tumor necrosis factor alpha (TNF-α) gene polymorphisms with clinical manifestations of dengue and TNF-α serum levels in a northwestern Mexican population. The study populations included dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, and a group of healthy controls (HCs) without history of dengue. Polymerase chain reaction-restriction fragment length polymorphism and Enzyme-Linked Immunosorbent Assay were performed to determine genotypes and serum concentration of TNF-α, respectively. There were no significant differences in alleles, genotypes, and haplotype frequencies between patients and HCs. However, when patients were separated into DF and DHF, there was an increased prevalence of the -308 GA genotype in HCs compared to DHF (odds ratio [OR] = 0.129, 95% confidence interval [CI] = 0.018-0.945, p = 0.025), as well as the GG haplotype (OR = 0.49, 95% CI = 0.273-0.880, p = 0.01757) in DF. The genotypes of both polymorphisms were not associated with hematologic manifestations. Serum TNF-α levels were significantly higher in patients than in HCs (p = 0.004). Our results suggest a minimal effect of the -308 and -238 TNF-α gene polymorphisms in dengue patients and that their increased serum levels of TNF-α are independent of genotypes.
为评估墨西哥西北部人群中肿瘤坏死因子α（TNF-α）基因-308和-238位点多态性与登革热临床表现及TNF-α血清水平的相关性。研究人群包括登革热（DF）患者、登革出血热（DHF）患者以及一组无登革热病史的健康对照（HCs）。分别采用聚合酶链反应-限制性片段长度多态性分析和酶联免疫吸附测定法来确定TNF-α的基因型和血清浓度。患者与健康对照在等位基因、基因型和单倍型频率上无显著差异。然而，当将患者分为DF和DHF时，与DHF相比，健康对照中-308 GA基因型的患病率增加（优势比[OR]=0.129，95%置信区间[CI]=0.018-0.945，p=0.025），在DF中GG单倍型的患病率也增加（OR=0.49，95%CI=0.273-0.880，p=0.01757）。两种多态性的基因型与血液学表现均无关联。患者的血清TNF-α水平显著高于健康对照（p=0.004）。我们的结果表明，TNF-α基因-308和-238位点多态性对登革热患者的影响极小，且他们血清中TNF-α水平的升高与基因型无关。
