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. 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.
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. sdunstan@oucru.org
S J
SJ
Dunstan
K A
KA
Rockett
N T N
NT
Quyen
Y Y
YY
Teo
C Q
CQ
Thai
N T
NT
Hang
A
A
Jeffreys
T G
TG
Clark
K S
KS
Small
C P
CP
Simmons
N
N
Day
S E
SE
O'Riordan
D P
DP
Kwiatkowski
J
J
Farrar
N H
NH
Phu
T T
TT
Hien
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology*; D008297:Male; D018512:Parasitemia / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014744:Vietnam; D055815:Young Adult
D015815:Cell Adhesion Molecules; C573420:ICAM1 protein, human; C448419:IL17RC protein, human; C508584:IL1A protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; D053582:Interleukin-1alpha; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1