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Title: Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1
Authors: Chiea Chuen Khor
Tran Nguyen Bich Chau
Junxiong Pang
Sonia Davila
Hoang Truong Long
Rick T.H. Ong
Sarah J. Dunstan
Bridget Wills
Jeremy Farrar
Ta Van Tram
Tran Thi Gan
Nguyen Thi Nguyet Binh
Le Trung Tri
Le Bich Lien
Nguyen Minh Tuan
Nguyen Thi Hong Tham
Mai Ngoc Lanh
Nguyen Minh Nguyet
Nguyen Trong Hieu
Nguyen Van N Vinh Chau
Tran Thi Thuy
Dennis E.K. Tan
Anavaj Sakuntabhai
Yik Ying Teo
Martin L. Hibberd
Cameron P. Simmons
Genome Institute of Singapore
National University of Singapore
Yong Loo Lin School of Medicine
Oxford University Clinical Research Unit
Nuffield Department of Clinical Medicine
Tien Giang Hospital
Sa Dec Hospital
Children's Hospital No. 1
Dong Thap Hospital
Hung Vuong Hospital
Children's Hospital No. 2
Institut Pasteur, Paris
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Nov-2011
Citation: Nature Genetics. Vol.43, No.11 (2011), 1139-1141
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. © 2011 Nature America, Inc. All rights reserved.
ISSN: 15461718
Appears in Collections:Scopus 2011-2015

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