UKPMC Funders Group Dengue shock syndrome at MICB and PLCE1

Abstract

Hypovolemic shock (Dengue shock syndrome (DSS)), is the commonest life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese follow-up sample of 1,737 cases and 2,934 controls. Polymorphisms within two genes showed genome-wide significant association with DSS (Pmeta = 4.41 × 10−11, per-allele odds ratio (OR) = 1.34 for MICB rs3132468 located within the broad MHC region and Pmeta = 3.08 × 10−10, per-allele OR = 0.80 for PLCE1 rs3765524). Our data implicates MICB is an important determinant in early immune control of dengue virus infection and PLCE1 a factor in vascular endothelial dysfunction and circulatory hypovolemia.