Single nucleotide polymorphism (rs1035130C>T) in the interleukin 18 receptor 1 gene and susceptibility to severe P. falciparum malaria in Lafia, North-central Nigeria

Abstract

The interleukin 18 receptor 1 (IL18R1) gene encodes a potent cytokine receptor that is critical for IL18 binding and subsequent signal transduction. This gene is a member of the IL1 receptor family that resides in a cluster of genes on human chromosome 2. Several polymorphisms have been shown to exist on this gene locus and some were found to be associated with inflammatory diseases but there is paucity of data on association with malaria. This study therefore, was aimed at determining the possible association of the rs1035130C>T coding polymorphism with severe malaria in Lafia, North-central Nigeria. The rs1035130C>T polymorphism was genotyped in a total of 214 participants including 98 severe malaria cases and 116 asymptomatic controls. DNA was extracted from blood spotted on filter paper using the QIAamp® DNA Mini Kit. The ABI PRISM® 3100 Genetic Analyzer was used to sequence the polymorphic locus. Our data showed a significantly higher frequency (P=0.021) of the CT heterozygous genotype in the asymptomatic control group (25.0%) than in the severe malaria group (13.27%). In addition, the frequency of the minor T allele was significantly higher (P=0.013) in the asymptomatic controls compared to the severe malaria cases. However, the TT homozygous genotype was not found in the severe malaria group. These results suggest a contributory role of the rs1035130C>T polymorphism in regulating host susceptibility or resistance to severe malaria and consequently have implications for understanding the molecular mechanisms of malaria pathogenesis.

Keywords: Malaria, Interleukin, rs1035130C>T, Polymorphism, Genotype.