Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese.
Sarah J. Dunstan,Kirk A. Rockett,Nguyen Than Ha Quyen,Yik Ying Teo,Cao Quang Thai,Nguyen T. Hang,Anne Jeffreys,Taane G. Clark,Kerrin S. Small,Cameron P. Simmons,Nicholas P. J. Day,Sean O’Riordan,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Jj J. Farrar,Nguyen Hoan Phu,Tran Tinh Hien +16 more
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TLDR
Variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese, and genotypes of rs708567 (IL17RC) correlate with parasitemia.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 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.read more
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Reappraisal of known malaria resistance loci in a large multicenter study.
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IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis.
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Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective.
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