Non-HLA gene polymorphisms and their implications on dengue virus infection

Abstract EN

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)-a, transforming growth factor (TGF)-b1, Fcc receptor II (FccRII), vitamin D receptor (VDR), interferon (IFN)-c, human platelet antigens (HPA), transporters associated with antigen processing (TAP), dendritic cell-specific ICAM3-grabbing non-integrin (DCSIGN) and Janus kinase 1 (JAK1), although some of these genes failed to show statistical significance.

Briefly, polymorphism in TNF-a, FccRII, CTLA-4, TGF-b1, 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 to be hospitalized during Cuban DENV epidemics [5].

Although pre-existing immunity may be a confounding factor, these reports argue strongly that genetic predisposition is an important factor as well.

Polymorphisms in cytokine regulatory gene regions have been described, some of these polymorphisms seem to correlate with its production, potentially conferring the flexibility to immune response.

The presence of certain genotypes influences the course of both viral and bacterial infections [7].

Variations in immune response as a consequence of polymorphisms in regulatory regions of cytokine genes and other genes may have influence on the DENV infection susceptibility and outcome [8].

In addition, genetic variants involved in viral entry and replication may play an important role in the causal pathway of DHF [9].

Here we have reviewed the implications of some non-human leukocyte antigen (HLA) gene polymorphisms to susceptibility, protection and severity of DENV infection based on publication from some of the countries.