-308G>A (rs1800629)and -244G>A(rs673) polymorphisms at the promoter region of the TNF-α gene in severe malaria patients in north-central Nigeria

Abstract

Tumour Necrosis Factor (TNF-α) is a multifunctional pro-inflammatory cytokine that has been shown to play an important role in the pathogenesis of malaria. The level of expression of this cytokine is however suggested to be under genetic control. This study evaluated the frequency of two single nucleotide polymorphisms (SNPs) at the promoter region of the TNF-α gene and their association with susceptibility to severe malaria in north-central Nigeria. A total of 201children (86 severe malaria cases and 115 asymptomatic controls) were recruited into the study. Blood sample was collected from each participant and DNA was isolated using the QIAamp^® DNA Mini Kit. Genotyping for SNPs was carried out using the ABI PRISM^® 3100 Genetic Analyzer. The distributions of the observed genotypes for the -308G>A (rs1800629) and -244G>A(rs673) polymorphismswere in conformity with the expected distribution when tested for Hardy-Weinberg equilibrium in the two groups. No significant difference (p>0.05) was found in the allelic distributions of the -308G>A and-244G>A between the severe malaria cases and the asymptomatic controls. The most common genotype in the study-population for the TNF-α (-308G>A and-244G>A) loci was homozygote GG. The AA homozygote genotype was not found in any of the study groups. However, a higher frequency of the -308GA and -244GA genotypes were found among individuals with severe malaria compared with the asymptomatic subjects although, this did not reach a statistically significant level (p=0.174; p=0.126 respectively).This study found no association of the TNF-α (-308G>A and -244G>A) polymorphisms with susceptibility to severe malaria. Further studies with larger population sizes are however needed to confirm this result.

Keywords: Malaria; cytokines; Plasmodium species; TNF-α; polymorphisms; PCR; north-central Nigeria