Open Access Research

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

Vinicius A Sortica1, Maristela G Cunha3, Maria Deise O Ohnishi4, Jose M Souza4, Ândrea KC Ribeiro-dos-Santos2, Ney PC Santos2, Sídia M Callegari-Jacques5, Sidney EB Santos2 and Mara H Hutz1*

Author Affiliations

1 Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

2 Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém, Pará, Brazil

3 Laboratório de Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

4 Programa de Ensaios Clínicos em Malária, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Ananindeua, Pará, Brazil

5 Departamento de Estatística, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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Malaria Journal 2012, 11:409  doi:10.1186/1475-2875-11-409

Published: 7 December 2012

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.

Keywords:
Malaria; Plasmodium vivax; Immune system polymorphisms; Brazilian amazon; IL1B; IL4R; IL12RB1; TNF