Host genetics and dengue fever

Xavier-Carvalho, Caroline; Cardoso, Cynthia Chester; Kehdy, Fernanda S. G.; Pacheco, Antônio Guilherme; Moraes, Milton Ozório

doi:10.1016/j.meegid.2017.11.009

Cited by 42 publications

(34 citation statements)

References 131 publications

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“…Regionspecific differences in patterns of care-seeking and criteria for hospitalization likely exist and may bias our comparisons; for example, individuals in Thailand may have been less likely to seek care for milder dengue illnesses as compared to individuals in Ecuador, and/or more likely to be hospitalized for a given clinical presentation. It is likely that human immunogenetic differences influence the clinical outcome to DENV infection and will differ across populations (29). Finally, undetected parasitic co-infections may play a role in modulating the immune response and thus the clinical outcome of DENV infection (30); for example, it is possible (but currently untested) that helminthic infections are more common in Ecuador than in Thailand and/or other parasitic co-infections such as Trypanosoma cruzi in the Americas may shape the clinical outcome of DENV infection.…”

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confidence: 99%

Key Findings and Comparisons From Analogous Case-Cluster Studies for Dengue Virus Infection Conducted in Machala, Ecuador, and Kamphaeng Phet, Thailand

Anderson

Stewart-Ibarra

Buddhari

et al. 2020

Front. Public Health

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Dengue viruses (DENV) pose a significant and increasing threat to human health across broad regions of the globe. Currently, prevention, control, and treatment strategies are limited. Promising interventions are on the horizon, including multiple vaccine candidates under development and a renewed and innovative focus on controlling the vector, Aedes aegypti. However, significant gaps persist in our understanding of the similarities and differences in DENV epidemiology across regions of potential implementation and evaluation. In this manuscript, we highlight and compare findings from two analogous cluster-based studies for DENV transmission and pathogenesis conducted in Thailand and Ecuador to identify key features and questions for further pursuit. Despite a remarkably similar incidence of DENV infection among enrolled neighborhood contacts at the two sites, we note a higher occurrence of secondary infection and severe illness in Thailand compared to Ecuador. A higher force of infection in Thailand, defined as the incidence of infection among susceptible individuals, is suggested by the higher number of captured Aedes mosquitoes per household, the increasing proportion of asymptomatic infections with advancing age, and the high proportion of infections identified as secondary-type infections by serology. These observations should be confirmed in long-term, parallel prospective cohort studies conducted across regions, which would advantageously permit characterization of baseline immune status (susceptibility) and contemporaneous assessment of risks and risk factors for dengue illness.

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confidence: 99%

Key Findings and Comparisons From Analogous Case-Cluster Studies for Dengue Virus Infection Conducted in Machala, Ecuador, and Kamphaeng Phet, Thailand

Anderson

Stewart-Ibarra

Buddhari

et al. 2020

Front. Public Health

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“…The vast majority of genetic studies for dengue have been candidate gene studies, where a number of genetic variants, including single nucleotide polymorphisms and HLA polymorphisms, have been implicated as genetic risk factors [12À19]. Existing data have been conflicting [20]. There has only been one genome-wide association study (GWAS) conducted for dengue, which showed an association between variants in major histocompatibility complex (MHC) class I polypeptide-related sequence B (MICB) and phospholipase C, epsilon 1 (PLCE1) and DSS [21].…”

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Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries

et al. 2020

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A B S T R A C TBackground: Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. Methods: We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. Findings: The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other.

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“… 1 , 5 Therefore, disease severity is a complex phenomenon and depends on numerous interactions between human genetic and immunological characteristics as well as viral factors. 1 , 6 , 7 …”

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confidence: 99%

“…The influence of the host genetic background in susceptibility to severe dengue has been evidenced for different populations using either candidate genes or genome-wide approaches. 6 A genome-wide association study has reported the association between MICB and PLCE genes and dengue shock syndrome in children from Vietnam. 8 Moreover, dengue outcomes have already been associated to HLA alleles as well as genes encoding the cell receptor DC-SIGN, CLEC5A , Fc receptors, and molecules such as CTLA-4, TGF-β and MBL-2.…”

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“… 8 Moreover, dengue outcomes have already been associated to HLA alleles as well as genes encoding the cell receptor DC-SIGN, CLEC5A , Fc receptors, and molecules such as CTLA-4, TGF-β and MBL-2. 6 , 7 However, conflicting results are still observed and the complete dissection of host genetic factors influencing dengue clinical course still depends on the development of independent studies including a careful control for genetic background.…”

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Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

Ornelas

Xavier-de-Carvalho

Alvarado-Arnez

et al. 2019

Mem. Inst. Oswaldo Cruz

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BACKGROUND Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.

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Host genetics and dengue fever

Cited by 42 publications

References 131 publications

Key Findings and Comparisons From Analogous Case-Cluster Studies for Dengue Virus Infection Conducted in Machala, Ecuador, and Kamphaeng Phet, Thailand

Key Findings and Comparisons From Analogous Case-Cluster Studies for Dengue Virus Infection Conducted in Machala, Ecuador, and Kamphaeng Phet, Thailand

Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

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