title: Genetic variants of MICB and PLCE1 and associations with non-severe dengue.
abstract: BACKGROUND
  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.
  
  
  METHODS
  3961 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.
  
  
  RESULTS
  Pooled 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom. james.whitehorn@lshtm.ac.uk
authors.forename: James
authors.initials: J
authors.lastname: Whitehorn
authors.forename: Tran Nguyen Bich
authors.initials: TN
authors.lastname: Chau
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Nguyet
authors.forename: Duong Thi Hue
authors.initials: DT
authors.lastname: Kien
authors.forename: Nguyen Than Ha
authors.initials: NT
authors.lastname: Quyen
authors.forename: Dinh The
authors.initials: DT
authors.lastname: Trung
authors.forename: Junxiong
authors.initials: J
authors.lastname: Pang
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Vinh Chau
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015395:Histocompatibility Antigens Class I; C098080:MICB antigen; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
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