Dados do Trabalho

Título

Evaluation of the influence of IL-2 -330 G/T (rs2069762) and IL-6 -572 G/C (rs1800796) polymorphisms on naturally acquired antibodies against components of the antimalarial vaccine candidate GMZ2 (GLURP and MSP-3)

Objetivo (s)

In the present study, we propose to investigate the functional Interleukin 2 (IL-2) -330 G/T (rs2069762) and Interleukin 6 (IL-6) -572 G/C (rs1800796) SNPs by evaluating their possible influence on antibody levels (total IgG and IgM) produced by naturally exposed populations in the Brazilian Amazon against Plasmodium falciparum antigenic proteins composing the antimalarial vaccine candidate GMZ2 (GLURP and MSP-3).

Material e Métodos

A total of 533 samples from the malaria-endemic areas of Cruzeiro do Sul and Mâncio Lima (Acre State) and Guajará (Amazonas State) were genotyped through qPCR using the TaqMan Genotyping Assay kit. The allelic and genotypic frequencies were determined through the TaqMan Genotyper software. The protein-specific antibody search was performed by ELISA using recombinant proteins corresponding to the R0 region of GLURP and the C-terminal region of MSP-3.

Resultados e Conclusão

Our data shows that (TT) was the most dominant IL-2 rs2069762 genotype with a frequency of 55.3% (295). The frequency of (GT) and (GG) genotypes was 39.2% (209) and 5.5% (29), respectively. The frequencies of the (T) and (G) alleles were 74.9% and 25.1%, respectively. Regarding IL-6 rs1800796, GG was the most dominant genotype with a frequency of 75.1% (400). The frequency of (GC) and (CC) genotypes was 22.1% (118) and 2.8% (15), respectively. The frequencies of the (G) and (C) alleles were 86.1% and 13.9%, respectively. Both rs2069762 and rs1800796 met the Hardy-Weinberg equilibrium principle (x² 1.0483 | p-value 0.5920) and (x² 2.9315 | p-value 0.2309), respectively. IgG and IgM antibodies against GLURP and MSP-3 were observed in 51.5% and 38% of the subjects, respectively. Our preliminary analysis showed that individuals bearing the IL-2 rs2069762 (GG) genotype presented higher levels of total IgG and IgM against GLURP. Increased IgG levels against MSP-3 were also observed in rs2069762 (GG) individuals, but no IgM difference was presented. As for the IL-6 rs1800796 SNP, higher levels of total IgG against GLURP and MSP-3 were also observed in homozygous mutant genotype individuals (CC). No IgM difference was presented as well. Early analysis taken together points to a possible influence of IL-2 rs2069762 (GG) and IL-6 (CC) rs1800796 genotypes against GLURP and MSP-3 humoral response levels. Further analysis will be conducted to evaluate possible individual allele associations.

Palavras-chave

GLURP; MSP-3; cytokine; SNP; genotyping; IgG; IgM; malaria; Plasmodium falciparum

Agradecimentos

FIOCRUZ, CNPq and FAPERJ