Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese
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....
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th-mahidol.136282018-06-11T12:06:08Z Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese S. J. Dunstan K. A. Rockett N. T N Quyen Y. Y. Teo C. Q. Thai N. T. Hang A. Jeffreys T. G. Clark K. S. Small C. P. Simmons N. Day S. E. O'Riordan D. P. Kwiatkowski J. Farrar N. H. Phu T. T. Hien Oxford University Clinical Research Unit Nuffield Department of Clinical Medicine Wellcome Trust Centre for Human Genetics National University of Singapore UCL London School of Hygiene & Tropical Medicine King's College London Mahidol University Wellcome Trust Sanger Institute Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Medicine 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 severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r 2 =0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings. © 2012 Macmillan Publishers Limited. All rights reserved. 2018-06-11T04:34:15Z 2018-06-11T04:34:15Z 2012-09-01 Article Genes and Immunity. Vol.13, No.6 (2012), 503-508 10.1038/gene.2012.25 14765470 14664879 2-s2.0-84865640798 https://repository.li.mahidol.ac.th/handle/123456789/13628 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84865640798&origin=inward |
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Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Medicine S. J. Dunstan K. A. Rockett N. T N Quyen Y. Y. Teo C. Q. Thai N. T. Hang A. Jeffreys T. G. Clark K. S. Small C. P. Simmons N. Day S. E. O'Riordan D. P. Kwiatkowski J. Farrar N. H. Phu T. T. Hien Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
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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 severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r 2 =0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings. © 2012 Macmillan Publishers Limited. All rights reserved. |
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Oxford University Clinical Research Unit |
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Oxford University Clinical Research Unit S. J. Dunstan K. A. Rockett N. T N Quyen Y. Y. Teo C. Q. Thai N. T. Hang A. Jeffreys T. G. Clark K. S. Small C. P. Simmons N. Day S. E. O'Riordan D. P. Kwiatkowski J. Farrar N. H. Phu T. T. Hien |
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Article |
author |
S. J. Dunstan K. A. Rockett N. T N Quyen Y. Y. Teo C. Q. Thai N. T. Hang A. Jeffreys T. G. Clark K. S. Small C. P. Simmons N. Day S. E. O'Riordan D. P. Kwiatkowski J. Farrar N. H. Phu T. T. Hien |
author_sort |
S. J. Dunstan |
title |
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
title_short |
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
title_full |
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
title_fullStr |
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
title_full_unstemmed |
Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese |
title_sort |
variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the vietnamese |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/13628 |
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1763490132803977216 |