Chacón-Duque Juan Camilo, Adhikari Kaustubh, Avendaño Efren, Campo Omer, Ramirez Ruth, Rojas Winston, Ruiz-Linares Andrés, Restrepo Berta Nelly, Bedoya Gabriel
Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia.
Department of Genetics, Evolution and Environment, University College London (UCL), London, UK.
Infect Genet Evol. 2014 Oct;27:89-95. doi: 10.1016/j.meegid.2014.07.003. Epub 2014 Jul 10.
The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies.
登革病毒（DENV）感染期间所表现出的严重程度差异很大，这可能受到宿主易感性的影响。在几种流行病学研究方法中，已发现某些种族群体之间的疾病结果存在差异，这表明人类遗传背景在疾病严重程度方面起着重要作用。在加勒比地区，据报道，与混血和白人自我报告群体相比，非洲裔人群中严重形式的出现频率要低得多。混合人群由于等位基因的变异和分布，例如那些与疾病易感性有关的等位基因，为遗传流行病学研究提供了优势，也有助于解释临床结果中的个体差异。当前的研究分析了三个哥伦比亚人群，与大多数拉丁美洲人群一样，这些人群是欧洲、美洲原住民和非洲祖先之间复杂混合过程的产物；主要目标是评估用30个祖先信息标记（AIMs）估计的遗传血统对DENV感染严重程度的影响。我们发现，在几种临床分类系统下非洲血统对严重后果具有保护作用：重症登革热（非洲血统每增加1%，比值比（OR）：0.963，95%置信区间（0.934 - 0.993），p值：0.016）、登革出血热（OR：0.969，95%置信区间（0.947 - 0.991），p值：0.006）以及出血的发生（OR：0.971，95%置信区间（0.952 - 0.989），p值：0.002）。相反，非洲血统从100%降至0%会显著增加严重后果的几率：重症登革热的OR为44倍，登革出血热为24倍，出血发生为20倍。此外，鉴于在DENV感染的特定阶段有更多证据，一些警示信号也显示出具有统计学意义的关联。这些结果提供了一致的证据，以便推断出为未来遗传流行病学和临床研究提供框架的统计模型。
