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Title: CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea
Authors: Hikota Osawa
Marita Troye-Blomberg
Kenji Hirayama
Mihoko Kikuchi
Francis Hombhanje
Takeo Tanihata
Rachanee Udomsangpetch
Anders Björkman
Takatoshi Kobayakawa
Akira Kaneko
Tokyo Women's Medical University
Karolinska Institutet
Stockholms universitet
Nagasaki University
University of Papua New Gunia
National Institute of Public Health Japan
Mahidol University
Keywords: Medicine
Issue Date: 1-Jan-2008
Citation: Tropical Medicine and Health. Vol.36, No.2 (2008), 93-100
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.
ISSN: 13494147
Appears in Collections:Scopus 2006-2010

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