Journal article
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese
SJ Dunstan, KA Rockett, NTN Quyen, YY Teo, CQ Thai, NT Hang, A Jeffreys, TG Clark, KS Small, CP Simmons, N Day, SE O'Riordan, DP Kwiatkowski, J Farrar, NH Phu, TT Hien
Genes and Immunity | NATURE PUBLISHING GROUP | Published : 2012
DOI: 10.1038/gene.2012.25
Open access
Abstract
The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with se..
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Awarded by Bill and Melinda Gates Foundation
Funding Acknowledgements
We would like to thank all the Vietnamese individuals who agreed to provide samples for this study. We acknowledge the work of the clinical staff from the Hospital of Tropical Diseases, HCMC and Phuoc Long and Dong Xoai District Hospitals in Binh Phuoc province, Vietnam, who initially diagnosed and studied the patients with severe malaria. We would like to thank Dr Nguyen Thi Hieu and his staff from Hung Vuong Obstetric Hospital for the collection of the cord blood controls. We thank the assistance of Susana Campino, Rachel Craik, Kate Rowlands, Angie Green and Christina Hubbart in the MalariaGEN resource centre in for the DNA handling and genotyping. We appreciate the contribution of the MalariaGEN ethics team (Oxford University, UK), especially Jantina de Vries. The clinical component of this study was funded through the Wellcome Trust Major Overseas Program in Vietnam (089276/Z/091Z). The MalariaGEN Project is supported by the Wellcome Trust (WT077383/Z/05/Z) and the Bill and Melinda Gates Foundation through the Foundations of the National Institutes of Health (grant number 566) as part of the Grand Challenges in Global Health Initiative. This research was also supported by the Medical Research Council (G0600718; G0600230). Dominic Kwiatkowski receives support from the Medical Research Council (G19/9). The Wellcome Trust also provides core awards to the Wellcome Trust Centre for Human Genetics (075491/Z/04; 090532/Z/09/Z) and to the Wellcome Trust Sanger Institute (077012/Z/05/Z and 098051).