IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women

Background: Tumour necrosis factor (TNF) and interferon gamma (IFN-gamma), encoded by TNF-836 C/A (rs 1800630) and IFN-gamma-1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. The aim of this study was to investigate the relationship between TNF-836 C/A and IFN-gamma-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women. Methods: A prospective cohort (cross-sectional) study was conducted in pregnant women attending the out-patient clinic in King Fahad Specialist Hospital in Jazan (KFSHJ), with a clinical diagnosis of malaria. A total of one hundred and eighty six pregnant women were genotyped for single nucleotide polymorphism (SNP) for TNF and IFN-gamma using Taqman (R) MGB Probes. Serum cytokine concentrations were measured by sandwich ELISA method. Results: A hospital case-control study of severe malaria in a Saudi population identified strong associations with individual single-nucleotide polymorphisms in the TNF and IFN-gamma genes, and defined TNF-836 C and IFN-gamma-1616 T genotypes and alleles which were statistically significantly associated with severe malaria infection. Furthermore, TNF-836 CC and IFN-gamma-1616 TT genotypes were associated with higher serum concentration of TNF and IFN-gamma, respectively, and with susceptibility to severe malaria. Conclusions: This data provides a starting point for functional and genetic analysis of the TNF and IFN-gamma genomic region in malaria infection affecting Saudi populations.