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

Amre Nasr,Osama Hamid,Gamal Allam,Abdelhamid Al-Ghamdi

doi:10.1186/1475-2875-13-314

Abstract

BackgroundTumour necrosis factor (TNF) and interferon gamma (IFN-γ), encoded by TNF-836 C/A (rs 1800630) and IFN-γ -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-γ-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women.MethodsA 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-γ using Taqman® MGB Probes. Serum cytokine concentrations were measured by sandwich ELISA method.ResultsA hospital case–control study of severe malaria in a Saudi population identified strong associations with individual single-nucleotide polymorphisms in the TNF and IFN-γ genes, and defined TNF-836 C and IFN-γ-1616 T genotypes and alleles which were statistically significantly associated with severe malaria infection. Furthermore, TNF-836 CC and IFN-γ-1616 TT genotypes were associated with higher serum concentration of TNF and IFN-γ, respectively, and with susceptibility to severe malaria.ConclusionsThis data provides a starting point for functional and genetic analysis of the TNF and IFN-γ genomic region in malaria infection affecting Saudi populations.

Highlights

Tumour necrosis factor (TNF) and interferon gamma (IFN-γ), encoded by TNF-836 C/A and IFN-γ -1616 C/T genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria
The second aim of this study was to investigate whether TNF −836 C/A and IFN-γ-1616 C/T genotypes and alleles frequency, are associated with susceptibility to either uncompleted or severe malaria infection among Saudi women living in the southern part of Saudi Arabia
Group III: Severe malaria patients (SM) [n = 64 (34.4%); median age of 20 with a range of (18–22) years] were malaria parasites positive and fulfilled one or more of the World Health Organization (WHO) criteria for severe P. falciparum [median of parasite density was 2,400 with a range of 2,000-2,800 parasite/μl) (Table 1)

Summary

Introduction

Tumour necrosis factor (TNF) and interferon gamma (IFN-γ), encoded by TNF-836 C/A (rs 1800630) and IFN-γ -1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. As there are over 85 million pregnant women at risk of P. falciparum infection every year [5], there is a need to better understand the mediators of poor clinical outcome of pregnancy-associated malaria (PAM) [6]. Both P. falciparum and P. vivax infections can cause adverse pregnancy outcomes, including maternal anaemia and LBW due to preterm delivery and foetal growth restriction, but the underlying mechanisms could differ [7]

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