TY - JOUR
T1 - Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria
T2 - A cohort study
AU - Omar, Ahmeddin H.
AU - Yasunami, Michio
AU - Yamazaki, Akiko
AU - Shibata, Hiroki
AU - Ofori, Michael F.
AU - Akanmori, Bartholomew D.
AU - Shuaibu, Mohammed Nasir
AU - Kikuchi, Mihoko
AU - Hirayama, Kenji
PY - 2012
Y1 - 2012
N2 - Background: In areas mesoendemic for malaria transmission, symptomatic individuals play a significant role as reservoirs for malaria infection. Understanding the pathogenesis of symptomatic malaria is important in devising tools for augmenting malaria control. In this study, the effect of TLR9 polymorphisms on susceptibility to symptomatic malaria was investigated among Ghanaian children. Methods: Four hundred and twenty nine (429) healthy Ghanaian children, aged three to eleven years (311 years), were enrolled into a cohort study and actively followed up for symptomatic malaria for one year. Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct sequencing, and their attributable and relative risks for symptomatic malaria determined. TLR9 haplotypes were inferred using the PHASE software and analysed for the risk of symptomatic malaria. A luciferase assay was performed to investigate whether the TLR9 haplotypes influence TLR9 promoter activity. Results: The rs352139 GG genotype showed a significantly increased relative risk of 4.8 for symptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P = 0.04). Conversely, the rs352140 GG genotype showed a significantly reduced relative risk of 0.34 (P = 0.048). TLR9 haplotypes analyses showed that TTAG haplotype was significantly associated with reduced relative risk of 0.2 for symptomatic malaria (P = 4×10-6) and a lower mean parasitaemia (0.007), while CTGA haplotype had an increased relative risk of 3.3 (P = 0.005). Functional luciferase reporter gene expression assay revealed that the TTA haplotype had a significantly higher promoter activity than the CCG, CTG and TCG haplotypes. Conclusions: Taken together, these findings indicate a significant association of TLR9 gene polymorphisms with symptomatic malaria among Ghanaian children in Dangme-West district.
AB - Background: In areas mesoendemic for malaria transmission, symptomatic individuals play a significant role as reservoirs for malaria infection. Understanding the pathogenesis of symptomatic malaria is important in devising tools for augmenting malaria control. In this study, the effect of TLR9 polymorphisms on susceptibility to symptomatic malaria was investigated among Ghanaian children. Methods: Four hundred and twenty nine (429) healthy Ghanaian children, aged three to eleven years (311 years), were enrolled into a cohort study and actively followed up for symptomatic malaria for one year. Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct sequencing, and their attributable and relative risks for symptomatic malaria determined. TLR9 haplotypes were inferred using the PHASE software and analysed for the risk of symptomatic malaria. A luciferase assay was performed to investigate whether the TLR9 haplotypes influence TLR9 promoter activity. Results: The rs352139 GG genotype showed a significantly increased relative risk of 4.8 for symptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P = 0.04). Conversely, the rs352140 GG genotype showed a significantly reduced relative risk of 0.34 (P = 0.048). TLR9 haplotypes analyses showed that TTAG haplotype was significantly associated with reduced relative risk of 0.2 for symptomatic malaria (P = 4×10-6) and a lower mean parasitaemia (0.007), while CTGA haplotype had an increased relative risk of 3.3 (P = 0.005). Functional luciferase reporter gene expression assay revealed that the TTA haplotype had a significantly higher promoter activity than the CCG, CTG and TCG haplotypes. Conclusions: Taken together, these findings indicate a significant association of TLR9 gene polymorphisms with symptomatic malaria among Ghanaian children in Dangme-West district.
KW - Cohort study
KW - Genetic polymorphism
KW - Genetic susceptibility
KW - Haplotype
KW - Luciferase promoter assay
KW - Symptomatic malaria
KW - TLR9
UR - http://www.scopus.com/inward/record.url?scp=84861038944&partnerID=8YFLogxK
U2 - 10.1186/1475-2875-11-168
DO - 10.1186/1475-2875-11-168
M3 - Article
C2 - 22594374
AN - SCOPUS:84861038944
SN - 1475-2875
VL - 11
JO - Malaria Journal
JF - Malaria Journal
M1 - 168
ER -