Laboratorio de Genética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín 050010, Colombia.
Instituto Colombiano de Medicina Tropical ICMT, Universidad CES, Sabaneta, Colombia.
J Infect Public Health. 2019 Jan-Feb;12(1):43-48. doi: 10.1016/j.jiph.2018.08.009. Epub 2018 Sep 15.
Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequencies and genetic associations may be influenced by the populational genetic background. Therefore, we performed a case-control study to evaluate possible associations between SNPs in IL4R and IL6R genes and clinical dengue in children from two Colombian populations.
We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP method, in 298 symptomatic children and 648 asymptomatic controls. Three individual genetic ancestral proportions (APs) (European, Amerindian, African) were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables gender, APs, and the population of origin were used like confusion variables.
We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R-rs8192284 AA genotype associated with clinical dengue in the pooled and Huila samples. Nevertheless, we found no association of these polymorphisms in the sample of Antioquia.
For the first time, we report SNPs in IL4R and IL6R genes associated with clinical dengue, which contributes to understanding the genetic susceptibility to dengue disease. Moreover, these results may be influenced by genetic background and must be evaluated through functional analysis.
病因学研究提供的证据表明,IL-4R 和 IL-6R 受体可能在临床登革热的发展的调节机制中发挥重要作用,尤其是在儿童中,儿童是具有高重症登革热风险的人群。此外,等位基因频率和遗传关联可能受人群遗传背景的影响。因此,我们进行了一项病例对照研究,以评估 IL4R 和 IL6R 基因中的 SNP 与来自两个哥伦比亚人群的儿童临床登革热之间的可能关联。
我们通过 PCR-RFLP 方法对 rs1805016(IL4R)和 rs8192284(IL6R)进行基因分型,共纳入 298 例有症状儿童和 648 例无症状对照。通过对 29 个 AIMs(祖先信息标记)进行基因分型,推断出三个个体遗传祖先比例(APs)(欧洲人、美洲印第安人、非洲人)。性别、APs 和来源人群等变量被用作混淆变量。
我们发现,在合并和 Huila 样本中,IL4R-rs1805016 GG 基因型和 G 等位基因携带者以及 IL6R-rs8192284 AA 基因型与临床登革热相关。然而,我们没有在 Antioquia 样本中发现这些多态性的关联。
这是首次报道 IL4R 和 IL6R 基因中的 SNP 与临床登革热相关,这有助于了解登革热疾病的遗传易感性。此外,这些结果可能受遗传背景的影响,必须通过功能分析进行评估。