Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1

Chiea Chuen Khor (1, 2) , Tran Nguyen Bich Chau (3) , Junxiong Pang (2, 1) , Sonia Davila (1, 2) , Hoang Truong Long (2, 3) , Rick T. H. Hong (1) , Sarah Dunstan (3, 4) , Bridget Wills (3, 4) , Jeremy Farrar (3, 4) , Ta van Tram (5) , Tran Thi Gan (5) , Nguyen Thi Nguyet Binh (6) , Le Trung Tri (6) , Le Bich Lien (7) , Nguyen Minh Tuan (7) , Nguyen Thi Hong Tham (8) , Mai Ngoc Lanh (8) , Nguyen Minh Nguyet (3) , Nguyen Trong Hieu (9) , Nguyen van Vinh Chau (10) , Tran Thi Thuy (11) , Dennis E. K. Tan (2) , Anavaj Sakuntabhai (12, 13) , Yik-Ying Teo (1, 2) , Martin L. Hibberd (2, 1) , Cameron P. Simmons (3, 4)

1 NUS - National University of Singapore
2 GIS - Genome Institute of Singapore
3 OUCRU - Oxford University Clinical Research Unit [Ho Chi Minh City]
4 Nuffield Department of Clinical Medicine [Oxford]
5 Tien Giang Hospital
6 Sa Dec Hospital
7 Children's Hospital No.1 [Ho Chi Minh City]
8 Dong Thap Hospital
9 Hung Vuong Hospital
10 Hospital for Tropical Diseases
11 Children's Hospital No. 2 [Ho Chi Minh City]
12 Génétique de la Réponse aux Infections chez l'Homme
13 Mahidol University [Bangkok]

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.

Domains: Genetics

Chiea Chuen Khor, Tran Nguyen Bich Chau, Junxiong Pang, Sonia Davila, Hoang Truong Long, et al.. Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1. Nature Genetics, 2011, 43 (11), pp.1139-1141. ⟨10.1038/ng.960⟩. ⟨pasteur-02069107⟩