ArticlePLoS neglected tropical diseases2018
Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
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- Admixture Mapping of Sepsis in European Individuals With African Ancestries.Frontiers in medicine · 2022Article
- SARS-CoV-2 infection in India bucks the trend: Trained innate immunity?American journal of human biology : the official journal of the Human Biology Council · 2021Article
- Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.Viruses · 2021Article
- Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease.Scientific reports · 2019Article
- Health Challenges of the Pacific Region: Insights From History, Geography, Social Determinants, Genetics, and the Microbiome.Frontiers in immunology · 2019Review
- Recent advances in understanding dengue.F1000Research · 2019Review
- Host genetic control of mosquito-borne Flavivirus infections.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.
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