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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Genetic polymorphisms associated with anti-malarial antibody levels in a low and unstable malaria transmission area in southern Sri Lanka

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Rajika L Dewasurendra, Prapat Suriyaphol, Sumadhya D Fernando, Richard Carter, Kirk Rockett, Patrick Corran, Dominic Kwiatkowski, Nadira D Karunaweera, in collaboration with the 7 MalariaGEN Consortium
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-281) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

RLD contributed by collecting samples and clinical information, DNA extraction, data analysis and manuscript preparation. PS contributed in support for data analysis. SDF contributed in designing and supervision of the project. RC was primarily involved in designing the project at the initial stage and critical review of the manuscript. KR contributed in genotyping, sequencing and review of the manuscript. PC contributed in ELISAs. DK contributed in supervision of the project and NDK with designing, supervision of the project and support for manuscript preparation. All authors read and approved the final manuscript.

Abstract

Background

The incidence of malaria in Sri Lanka has significantly declined in recent years. Similar trends were seen in Kataragama, a known malaria endemic location within the southern province of the country, over the past five years. This is a descriptive study of anti-malarial antibody levels and selected host genetic mutations in residents of Kataragama, under low malaria transmission conditions.

Methods

Sera were collected from 1,011 individuals residing in Kataragama and anti-malarial antibodies and total IgE levels were measured by a standardized ELISA technique. Host DNA was extracted and used for genotyping of selected SNPs in known genes associated with malaria. The antibody levels were analysed in relation to the past history of malaria (during past 10 years), age, sex, the location of residence within Kataragama and selected host genetic markers.

Results

A significant increase in antibodies against Plasmodium falciparum antigens AMA1, MSP2, NANP and Plasmodium vivax antigen MSP1 in individuals with past history of malaria were observed when compared to those who did not. A marked increase of anti-MSP1(Pf) and anti-AMA1(Pv) was also evident in individuals between 45–59 years (when compared to other age groups). Allele frequencies for two SNPs in genes that code for IL-13 and TRIM-5 were found to be significantly different between those who have experienced one or more malaria attacks within past 10 years and those who did not. When antibody levels were classified into a low-high binary trait, significant associations were found with four SNPs for anti-AMA1(Pf); two SNPs for anti-MSP1(Pf); eight SNPs for anti-NANP(Pf); three SNPs for anti-AMA1(Pv); seven SNPs for anti-MSP1(Pv); and nine SNPs for total IgE. Eleven of these SNPs with significant associations with anti-malarial antibody levels were found to be non–synonymous.

Conclusions

Evidence is suggestive of an age–acquired immunity in this study population in spite of low malaria transmission levels. Several SNPs were in linkage disequilibrium and had a significant association with elevated antibody levels, suggesting that these host genetic mutations might have an individual or collective effect on inducing or/and maintaining high anti–malarial antibody levels.
Zusatzmaterial
Additional file 1: Optical Density (OD) values for each sample tested for the six antibodies and the total IgE levels and the Corresponding antibody titres and levels OD was measured at 492 nm in an ELISA reader. (XLS 303 kb) (XLS 304 KB)
12936_2012_2193_MOESM1_ESM.xls
Additional file 2: Tested Single Nucleotide Polymorphisms (SNPs) and their relevant details. (XLS 48 kb) (XLS 48 KB)
12936_2012_2193_MOESM2_ESM.xls
Authors’ original file for figure 1
12936_2012_2193_MOESM3_ESM.pdf
Authors’ original file for figure 2
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Authors’ original file for figure 3
12936_2012_2193_MOESM5_ESM.doc
Authors’ original file for figure 4
12936_2012_2193_MOESM6_ESM.doc
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