Acioli-Santos Bartolomeu, Segat Ludovica, Dhalia Rafael, Brito Carlos A A, Braga-Neto Ulisses M, Marques Ernesto T A, Crovella Sergio
Virology and Experimental Therapy Laboratory, Aggeu Magalhães Research Center-CPqAM/FIOCRUZ, Recife, Brazil.
Hum Immunol. 2008 Feb;69(2):122-8. doi: 10.1016/j.humimm.2008.01.005. Epub 2008 Feb 12.
Dengue disease can clinically evolve from an asymptomatic and mild disease, known as dengue fever (DF), to a severe disease known as dengue hemorrhagic fever (DHF). Recent evidence has shown how host genetic factors can be correlated with severe dengue susceptibility or protection. Many of these genes, such as CD209, TNF-a, vitamin D receptor, and FC gamma receptor IIA, are components of the innate immune system, suggesting that innate responses might have a role in dengue pathogenesis. MBL2 gene polymorphisms have been shown to modulate susceptibility or protection in many viral diseases. We investigated the involvement of MBL2 gene in the dengue clinical outcome through the analysis of MBL2 exon 1 polymorphisms (at codons 52, 54, and 57) known to be associated with reduced serum levels of the MBL protein. The genotypes of 110 well-characterized dengue-positive patients were statistically analyzed to establish possible correlations between MBL2 polymorphisms and parameters such as sex, type of infection (primary or secondary response), race/ethnicity, course of infection, and age. We found significant correlations between wild-type AA MBL2 genotype and age as associated risk factors for development of dengue-related thrombocytopenia.
登革热疾病在临床上可从无症状和轻症,即登革热(DF),发展为重症,即登革出血热(DHF)。最近的证据表明宿主遗传因素如何与严重登革热易感性或保护性相关。其中许多基因,如CD209、TNF-α、维生素D受体和Fcγ受体IIA,都是先天免疫系统的组成部分,这表明先天反应可能在登革热发病机制中起作用。MBL2基因多态性已被证明可调节许多病毒疾病的易感性或保护性。我们通过分析已知与MBL蛋白血清水平降低相关的MBL2外显子1多态性(第52、54和57密码子),研究了MBL2基因在登革热临床结局中的作用。对110例特征明确的登革热阳性患者的基因型进行统计学分析,以确定MBL2多态性与性别、感染类型(初次或二次反应)、种族/民族、感染病程和年龄等参数之间可能存在的相关性。我们发现野生型AA MBL2基因型与年龄之间存在显著相关性,它们是登革热相关血小板减少症发生的相关危险因素。