Publication: CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea
Issued Date
2008-01-01
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ISSN
13494147
13488945
13488945
Other identifier(s)
2-s2.0-85024744668
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Mahidol University
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SCOPUS
Bibliographic Citation
Tropical Medicine and Health. Vol.36, No.2 (2008), 93-100
Suggested Citation
Hikota Osawa, Marita Troye-Blomberg, Kenji Hirayama, Mihoko Kikuchi, Francis Hombhanje, Takeo Tanihata, Rachanee Udomsangpetch, Anders Björkman, Takatoshi Kobayakawa, Akira Kaneko CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea. Tropical Medicine and Health. Vol.36, No.2 (2008), 93-100. doi:10.2149/tmh.2008-07 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/19838
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Title
CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea
Abstract
In malaria endemic areas, people naturally acquire an age-related immunity to malaria. Part of this immunity involves anti-malarial specific antibodies. Acquisition of these malaria-specific antibodies depends not only on exposure to malaria parasites but also on the human genetic predisposition. CTLA-4 is a costimulatory molecule that delivers an inhibitory signal to suppress T-cell as well as B-cell responses. We investigated associations between malaria-specific antibody levels and CTLA-4 polymorphisms in 189 subjects living in a hyper-endemic area of Papua New Guinea (PNG), where both P. falciparum and P. vivax are prevalent. We determined P. falciparum /P. vivax specific IgG/IgE levels (Pf-IgG, Pv-IgG, Pf-IgE, Pv-IgE) and polymorphisms in the CTLA-4 gene at position -1661 promoter region (A/G), the +49 exon 1 non-synonymous mutation (A/G), and the +6230 3'-UTR (A/G). All quantified antibody levels were significantly higher in subjects > 5 years (n = 150) than in subjects ≤ 5 years of age (n = 39). In children ≤ 5 years old, significant associations were detected between CTLA-4 +49 (GG/AG vs. AA) and Pv-IgG (median 18.7 vs. 13.7 μg/ml, P = 0.017) and Pv-IgE (266.6 vs. 146.5 pg/ml, P = 0.046). No significant difference was observed in subjects > 5 years old. These results suggest that the CTLA-4+49 polymorphism influenced Pv-IgG and Pv-IgE levels among children less than five years old in the studied population, which may regulate the age- and species-specific clinical outcomes of malaria infection. © 2008, Japanese Society of Tropical Medicine. All rights reserved.