Genetic Variants of <em>MICB</em> and <em>PLCE1</em> and Associations with Non-Severe Dengue

<div><p>Background</p><p>A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at <i>MICB</i> rs3132468 and <i>PLCE1</i> rs3740360. The aim of this study was to define the extent to which <i>MICB</i> (rs3132468) and <i>PLCE1</i> (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue.</p> <p>Methods</p><p>3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at <i>MICB</i> rs3132468 and <i>PLCE1</i> 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.</p> <p>Results</p><p>Pooled analysis of the paediatric and adult cohorts indicated a significant association between <i>MICB</i> rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 – 1.24; <i>P</i> = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and <i>PLCE1</i> rs3740360 (OR = 0.92; 95%CI: 0.85 – 0.99; <i>P</i> = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for <i>MICB</i> rs3132468 and OR = 0.75, <i>P</i> = 0.041 for <i>PLCE1</i> rs3740360) and dengue in infants.</p> <p>Discussion</p><p>This study confirms that the <i>MICB</i> rs3132468 and <i>PLCE1</i> 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.</p>