Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study
Abstract 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 TL...
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ftdoajarticles:oai:doaj.org/article:b5e3df2afd034d92a3776a5008c623ff 2023-05-15T15:16:10+02:00 Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study Omar Ahmeddin H Yasunami Michio Yamazaki Akiko Shibata Hiroki Ofori Michael F Akanmori Bartholomew D Shuaibu Mohammed Kikuchi Mihoko Hirayama Kenji 2012-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-168 https://doaj.org/article/b5e3df2afd034d92a3776a5008c623ff EN eng BMC http://www.malariajournal.com/content/11/1/168 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-168 1475-2875 https://doaj.org/article/b5e3df2afd034d92a3776a5008c623ff Malaria Journal, Vol 11, Iss 1, p 168 (2012) Cohort study TLR9 Symptomatic malaria Genetic susceptibility Genetic polymorphism Haplotype Luciferase promoter assay Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-168 2022-12-31T01:09:53Z Abstract 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 (3–11 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 168 |
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Cohort study TLR9 Symptomatic malaria Genetic susceptibility Genetic polymorphism Haplotype Luciferase promoter assay Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Cohort study TLR9 Symptomatic malaria Genetic susceptibility Genetic polymorphism Haplotype Luciferase promoter assay Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Omar Ahmeddin H Yasunami Michio Yamazaki Akiko Shibata Hiroki Ofori Michael F Akanmori Bartholomew D Shuaibu Mohammed Kikuchi Mihoko Hirayama Kenji Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
topic_facet |
Cohort study TLR9 Symptomatic malaria Genetic susceptibility Genetic polymorphism Haplotype Luciferase promoter assay Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract 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 (3–11 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. |
format |
Article in Journal/Newspaper |
author |
Omar Ahmeddin H Yasunami Michio Yamazaki Akiko Shibata Hiroki Ofori Michael F Akanmori Bartholomew D Shuaibu Mohammed Kikuchi Mihoko Hirayama Kenji |
author_facet |
Omar Ahmeddin H Yasunami Michio Yamazaki Akiko Shibata Hiroki Ofori Michael F Akanmori Bartholomew D Shuaibu Mohammed Kikuchi Mihoko Hirayama Kenji |
author_sort |
Omar Ahmeddin H |
title |
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
title_short |
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
title_full |
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
title_fullStr |
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
title_full_unstemmed |
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study |
title_sort |
toll-like receptor 9 (tlr9) polymorphism associated with symptomatic malaria: a cohort study |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-168 https://doaj.org/article/b5e3df2afd034d92a3776a5008c623ff |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 168 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/168 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-168 1475-2875 https://doaj.org/article/b5e3df2afd034d92a3776a5008c623ff |
op_doi |
https://doi.org/10.1186/1475-2875-11-168 |
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Malaria Journal |
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11 |
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168 |
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1766346466243117056 |