title: Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1.
abstract: Hypovolemic shock (dengue shock syndrome (DSS)) is the most common 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 sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.
authors: Infectious Diseases, Genome Institute of Singapore, Singapore.
authors: Chiea Chuen
authors: CC
authors: Khor
authors: Tran Nguyen Bich
authors: TN
authors: Chau
authors: Junxiong
authors: J
authors: Pang
authors: Sonia
authors: S
authors: Davila
authors: Hoang Truong
authors: HT
authors: Long
authors: Rick T H
authors: RT
authors: Ong
authors: Sarah J
authors: SJ
authors: Dunstan
authors: Bridget
authors: B
authors: Wills
authors: Jeremy
authors: J
authors: Farrar
authors: Ta
authors: T
authors: Van Tram
authors: Tran Thi
authors: TT
authors: Gan
authors: Nguyen Thi Nguyet
authors: NT
authors: Binh
authors: Le Trung
authors: le T
authors: Tri
authors: Le Bich
authors: le B
authors: Lien
authors: Nguyen Minh
authors: NM
authors: Tuan
authors: Nguyen Thi Hong
authors: NT
authors: Tham
authors: Mai Ngoc
authors: MN
authors: Lanh
authors: Nguyen Minh
authors: NM
authors: Nguyet
authors: Nguyen Trong
authors: NT
authors: Hieu
authors: Nguyen
authors: N
authors: Van N Vinh Chau
authors: Tran Thi
authors: TT
authors: Thuy
authors: Dennis E K
authors: DE
authors: Tan
authors: Anavaj
authors: A
authors: Sakuntabhai
authors: Yik-Ying
authors: YY
authors: Teo
authors: Martin L
authors: ML
authors: Hibberd
authors: Cameron P
authors: CP
authors: Simmons
mesh_terms: D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; 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