Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Jun 22;18(1):282.
doi: 10.1186/s12879-018-3186-6.

Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis

Megan E Cahill  1 , Samantha Conley  2 , Andrew T DeWan  1 , Ruth R Montgomery  3
Affiliations
Meta-Analysis

Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis

Megan E Cahill et al. BMC Infect Dis. .

Abstract

Background: Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions.

Methods: We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified.

Results: We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR = 0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR = 1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR = 2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR = 0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR = 1.54, 95% CI: 1.02-2.31), and IFN-γ (meta-OR = 2.48, 95% CI: 1.30-4.71), is associated with dengue disease.

Conclusions: Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.

Keywords: Dengue virus; Disease severity; Genetic variation; Meta-analysis; Single nucleotide polymorphism; West Nile virus.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable. Data sets were extracted without personal identifiers and organized into literature tables.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
PRISMA Flowchart of strategy to identify papers assessing genetic variation and WNV or DENV disease
Fig. 2
Fig. 2
Significant meta-ORs for associations between OAS1 (rs10774671) and CCR5 (Δ32) and West Nile virus disease. Genotype count data from published reports of WNV subjects were meta-analyzed using RevMan. The meta-odds ratio (OR) for more severe disease is indicated with the genetic model for each gene. For each gene, the allele or genotype is shown which is associated with asymptomatic infection and controls (blue) or severe disease (yellow) outcome
Fig. 3
Fig. 3
Meta-analyzed genetic variation associated with DENV disease. Genotype count data from published reports of WNV subjects were meta-analyzed using RevMan. The meta-odds ratio (OR) for more severe disease is indicated with the genetic model for each gene: MBL2 (a), IFN-γ (b), MICB (c), PLCE1 (d and e). If multiple models were significant, we present the most significant model. The alleles or genotypes associated with asymptomatic infection and controls (blue) or with severe disease (yellow) outcome are shown for each gene
See this image and copyright information in PMC

References

    1. Papa A, Karabaxoglou D, Kansouzidou A. Acute West Nile virus neuroinvasive infections: cross-reactivity with dengue virus and tick-borne encephalitis virus. J Med Virol. 2011;83(10):1861–1865. doi: 10.1002/jmv.22180. - DOI - PubMed
    1. Hua RH, Chen NS, Qin CF, Deng YQ, Ge JY, Wang XJ, Qiao ZJ, Chen WY, Wen ZY, Liu WX, et al. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese encephalitis virus: potential application in the detection of antibodies to distinguish Japanese encephalitis virus infection from West Nile virus and dengue virus infections. Virol J. 2010;7:249. doi: 10.1186/1743-422X-7-249. - DOI - PMC - PubMed
    1. Daep CA, Munoz-Jordan JL, Eugenin EA. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus. J Neuro-Oncol. 2014;20(6):539–560. - PMC - PubMed
    1. Gubler DJ. The continuing spread of West Nile virus in the western hemisphere. Clin Infect Dis. 2007;45(8):1039–1046. doi: 10.1086/521911. - DOI - PubMed
    1. Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA. 2013;310(3):308–315. doi: 10.1001/jama.2013.8042. - DOI - PMC - PubMed

MeSH terms