Non-HLA gene polymorphisms and their implications on dengue virus infection
a Tropical and Infection Diseases
Division, Internal Medicine Department, School of Medicine, Syiah Kuala
University, Banda Aceh, Indonesia
b Post-graduate Program, Immunology Department, Airlangga University, Surabaya, Indonesia
b Post-graduate Program, Immunology Department, Airlangga University, Surabaya, Indonesia
Abstract
Exposure to
the dengue virus (DENV) evokes a variety of genetically-controlled
immunological responses. Genetic variants involved in viral entry, replication
and innate immunity pathways play an important role in the causal pathway of
dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Here we have reviewed
implications of some genetic polymorphisms of the pathways related to DENV
infection susceptibility, protection and severity. Large case-control studies
examining a variety of single-nucleotide polymorphisms (SNPs) in a variety of
genes have been performed in DENV patients in some countries. SNP gene
candidates that have shown associations with DENV infection are mannose-binding
lectin (MBL), interleukin (IL)-4, IL-6, IL-10, interleukin-1 receptor
antagonist (IL-1RA), toll-like receptor 4 (TLR4), cytotoxic T-lymphocyte
antigen 4 (CTLA-4), tumor necrosis factor (TNF)-α, transforming growth factor
(TGF)-β1, Fcγ receptor II (FcγRII), vitamin D receptor (VDR), interferon
(IFN)-γ, human platelet antigens (HPA), transporters associated with antigen
processing (TAP), dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)
and Janus kinase 1 (JAK1), although some of these genes failed to show statistical
significance. Briefly, polymorphism in TNF-α, FcγRII, CTLA-4, TGF-β1, HPA,
DC-SIGN, TAP and JAK1 genes has been associated with DHF/DSS development.
Polymorphism in MBL2 gene was shown to be associated with thrombocytopenia and
increased risk of DHF development. In contrary, polymorphism in VDR gene shows
moderate associations with resistance to the most severe form of DHF. However,
neutral associations have been reported for IL-4 promoters, IL-1RA, IFN-γ,
IL-6, TLR4 and IL-10 gene polymorphism. In conclusion, there are strong
evidences from several epidemiological studies indicating host genetic factors
as important components in DENV infection susceptibility, protection and
severity. © 2012.
Full Text :
Tidak ada komentar:
Posting Komentar