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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Vinicius A Sortica, Maristela G Cunha, Maria Deise O Ohnishi, Jose M Souza, Ândrea KC Ribeiro-dos-Santos, Ney PC Santos, Sídia M Callegari-Jacques, Sidney EB Santos, Mara H Hutz
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-409) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

VAS designed the research project, carried out the laboratory assays, and wrote the manuscript; MGC participated in the study design, planning and data collection, revised the manuscript for important intellectual content and approved the version to be published; MDOO participated in the study design, planning and data collection, performed the malaria diagnosis and revised the manuscript for important intellectual content and approved the version to be published; JMS participated in the study design, planning and data collection, performed the malaria diagnosis and revised the manuscript for important intellectual content and approved the version to be published; NPCS participated in the study design, planning and data collection, performed the malaria diagnosis and revised the manuscript for important intellectual content and approved the version to be published; AKCR participated in the study design, planning and data collection, revised the manuscript for important intellectual content and approved the version to be published; SMC-J participated in the study design, planning and performed the statistical analysis and approved the version to be published; SEBS genotyped the ancestry informative markers, revised the manuscript for important intellectual content, and approved the version to be published; MHH conceived the study, and participated in its design and coordination, analysed the data, and wrote the final version of the article. All authors read and approved the final manuscript.

Abstract

Background

Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood.

Methods

The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test.

Results

The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively).

Conclusion

Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.
Zusatzmaterial
Additional file 1: Table S1. List of SNPs investigated in the present study. List of SNPs investigated, their location in the gene, pubmed database SNP identification, manufacturer’s assay identification and allele frequencies in case and control groups. (PDF 134 KB)
12936_2012_2568_MOESM1_ESM.pdf
Additional file 2: Table S2. Control and malaria group genotypic frequencies. Genotypic frequencies of all SNPs in case and control groups. (PDF 183 KB)
12936_2012_2568_MOESM2_ESM.pdf
Additional file 3: Table S3. Poisson Regression for association between malaria and control samples controlling for age. Poisson Regression results for association between malaria and control samples controlling for age. (PDF 114 KB)
12936_2012_2568_MOESM3_ESM.pdf
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