HLA and other gene associations with dengue disease severity.
Large case control gene association studies have been performed on cohorts of dengue virus (DENV) infected patients identified in mainland Southeast Asia, South Asia and the Caribbean. Candidate genes that have shown statistically significant associations with DENV disease severity encode HLA molecules, cell receptors for IgG (FcGII), vitamin D and ICAM3 (DCSIGN or CD209), pathogen recognition molecules such as mannose binding lectin (MBL), blood related antigens including ABO and human platelet antigens (HPA1 and HPA2). In ethnic Thais with secondary infections a variety of HLA class I alleles (HLA-A 0203, 0207, A11, B 15, B 44, B 46, B 48, B 51, B 52), DCSIGN promoter polymorphisms and the AB blood group, independently associate with either susceptibility or resistance to dengue fever (DF) and the more severe dengue hemorrhagic fever (DHF). There is also evidence that some HLA associations with disease severity correlate with the DENV serotype inducing secondary infections. Taken together, there is now evidence that allelic variants of multiple gene loci involved in both acquired and innate immune responses contribute significantly to DENV disease outcome and severity. Further analysis of the genetic basis of severe DENV disease in different at risk populations may contribute to the development of new preventative and therapeutic interventions.
Centre for Nephrology & The Anthony Nolan Trust, University College London, The Royal Free Hospital Campus, Rowland Hill Street, London, NW3 2PF, UK. h.stephens@ucl.ac.uk
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D000017:ABO Blood-Group System / Q000235:genetics; D000483:Alleles; D016824:Antigens, Human Platelet / Q000235:genetics; D001210:Asia, Southeastern / Q000453:epidemiology; D017691:Caribbean Region / Q000453:epidemiology; D015815:Cell Adhesion Molecules / Q000235:genetics; D003715:Dengue / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D003716:Dengue Virus; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D054884:Host-Pathogen Interactions; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D037601:Mannose-Binding Lectin / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics; D012720:Severity of Illness Index; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000017:ABO Blood-Group System; D016824:Antigens, Human Platelet; D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin