Avendaño-Tamayo Efren, Campo Omer, Chacón-Duque Juan Camilo, Ramírez Ruth, Rojas Winston, Agudelo-Flórez Piedad, Bedoya Gabriel, Restrepo Berta Nelly
Grupo de Genética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín, Colombia Departamento de Ciencias Básicas, Tecnológico de Antioquia - Institución Universitaria, Medellín, Colombia.
Biomedica. 2017 Dec 1;37(4):486-497. doi: 10.7705/biomedica.v37i4.3305.
The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines.
To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population.
We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chi-square and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component.
The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components.
The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.
宿主的基因构成会影响登革热的临床症状。这可能是由于编码促炎细胞因子的基因变异所产生的影响。
在哥伦比亚人群样本中,评估肿瘤坏死因子α(TNFA)、白细胞介素6(IL6)和干扰素γ(IFNG)候选基因中三种多态性变异与登革热严重程度之间的关联。
我们分别在226例登革热感染患者中评估了TNFA、IL6和IFNG候选基因中的rs1800750、rs2069843和rs2069705多态性。采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)技术对基因型进行分型。为了确定不同登革热表型的风险,我们使用卡方检验比较等位基因频率,并使用逻辑回归分析基因型和单倍型。最后,这些分析通过自我识别或祖先遗传成分的数据进行校正。
经自我识别校正后,rs2069843多态性中的A等位基因与非裔哥伦比亚人的登革出血热病例相关。在整个样本中,经祖先遗传成分校正后,这种多态性具有可重复性。此外,在登革出血热患者中,无论是否经祖先遗传成分校正,rs1800750、rs2069843和rs2069705的GGT和GAC等位基因组合之间均存在显著关联。此外,无论欧洲、美洲印第安人和非洲遗传成分如何,AGC等位基因组合产生的白细胞介素-6比GGC组合多58.03 pg/ml。
TNFA、IL6和IFNG基因中rs1800750、rs2069843和rs2069705的GGT和GAC多态性变异分别与哥伦比亚人群样本中登革热严重程度的易感性相关。