Background and aims Tumour necrosis factor-α (TNF-α) is a proinflammatory cytokine associated with P. falciparum malaria and autoimmune disorders. Elevated plasma TNF-a has been linked to P. falciparum malarial severity and mortality. Higher levels of TNF-α has also been reported in systemic lupus erythematosus (SLE). Two functional common polymorphisms (G-238A and G-308A) at promoter region of TNF-α gene have been linked to SLE susceptibility in different population. In the present report, we conducted a case control study to investigate association of TNF-α (G-238A and G-308A) polymorphisms with susceptibility/resistance to SLE development in a P. falciparum malaria endemic cohort.

Methods A total of 204 female SLE patients and 224 age and sex matched healthy controls were enrolled in the study. TNF-α polymorphisms (G-238A and G-308A) were typed by polymerase chain reaction and restriction length polymorphism (PCR-RFLP). Plasma level of TNF-a was quantified by enzyme linked immunosorbent assay.

Results The prevalence of heterozygous mutants and minor alleles of TNF-α (G-238A and G-308A) polymorphisms were significantly higher in SLE patients compared to healthy controls. Furthermore, heterozygous (GA) and minor allele (A) of TNF-α (G-238A) polymorphism were associated with susceptibility to lupus nephritis. SLE patients displayed higher levels of plasma TNF-α compared to healthy controls. TNF-α (G-238A and G-308A) variants were associated with higher plasma TNF-α in both SLE patients and healthy control.

Conclusions The results of the present study demonstrate that TNF-α (G-238A and G-308A) variants are associated with higher plasma TNF-α level and increased susceptibility to development of SLE in malarial endemic areas.