Role of IL6, IL12B and VDR gene polymorphisms in Plasmodium vivax malaria severity, parasitemia and gametocytemia levels in an Amazonian Brazilian population.

ABSTRACT

OBJECTIVE: To investigate the influence of IL6, IL12B and VDR single nucleotide polymorphisms (SNPs) in uncomplicated Plasmodium vivax infection symptoms intensity, parasitemia and gametocytemia levels in a Brazilian Amazonian population. METHODS: A total of 167 malaria patients infected by P. vivax have parasitemia and gametocytemia levels estimated before treatment. Fourteen clinical symptoms were evaluated and included in a principal component analysis to derive a clinical symptom index. Patients were genotyped for IL6-174C>G, IL12B 735T>C, 458A>G, 159A>C, and VDR FokI, TaqI, BsmI SNPs by Taqman 5' nuclease assays. A General Linear Model analysis of covariance with age, gender, exposure period and infection history and genetic ancestry was performed to investigate the association of genotypes with parasitemia and gametocytemia levels and with a clinical symptom index. RESULTS: Higher parasitemia levels were observed in IL6-174C carriers (p=0.02) whereas IL12B CGT haplotype carriers presented lower parasitemia levels (p=0.008). VDR TaqIC/BsmIA haplotype carriers showed higher gametocyte levels than non-carriers (p=0.013). Based on the clinical index values the IL6-174C>G polymorphism was associated with malaria severity. The IL6-174C carriers presented a more severe clinical index when compared to GG homozygotes (p=0.001). CONCLUSION: The present study suggests that IL6, IL12 and VDR influence severity, parasitemia and gametocytemia clearance in P. vivax infections, and highlights their potential role in malaria immune response in an Amazonian population.