Abstract
BackgroundA recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue.Methods3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model.ResultsPooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 – 1.24; P = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR = 0.92; 95%CI: 0.85 – 0.99; P = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for MICB rs3132468 and OR = 0.75, P = 0.041 for PLCE1 rs3740360) and dengue in infants.DiscussionThis study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis.
Highlights
Dengue is the most important arboviral disease of humans.[1]
Across the 7 cohorts (4 pediatric and 3 adult) there were 297 dengue shock syndrome (DSS) cases (161 pediatric and 136 adult), 3500 non-DSS dengue cases (2759 pediatric and 741 adult cases), and 164 cases of infants with dengue that were successfully genotyped at MHC class I polypeptide-related sequence B (MICB) rs3132468 and PLCE1 rs3740360
MICB rs3132468 and PLCE1 rs3740360 genotypes are associated with DSS in Vietnamese children.[6]
Summary
Dengue is the most important arboviral disease of humans.[1]. Dengue viruses (DENV) cause a spectrum of clinical manifestations ranging from asymptomatic infection through to lifethreatening shock and haemorrhage.[1,2] The clinical outcome of an individual infection is influenced by a variety of virus and host-related factors. The host factors that influence the clinical course of an individual infection include flavivirus infection history, host genotype, sex, age, and the presence of underlying medical conditions.[3,4,5] The first GWAS in dengue identified susceptibility loci for dengue shock syndrome (DSS) at MHC class I polypeptide-related sequence B (MICB) (C/T, rs3132468) on chromosome 6 and phospholipase C, epsilon 1 (PLCE1) (C/A, rs3740360) on chromosome 10.[6] The MICB gene encodes an activating ligand of natural killer (NK) cells (and possibly CD8+ T cells). A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue
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