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304 Tnf-Α promoter polymorphisms (g-238a and g-308a) are associated with susceptibility to systemic lupus erythematosus: a study in p. falciparum endemic area
  1. AK Panda1,
  2. H Mahato1,
  3. R Tripathy2 and
  4. BK Das3
  1. 1Central University of Jharkhand, Centre for Life Sciences, Ranchi, India
  2. 2SCB Medical College, Department of Biochemistry, cuttack, India
  3. 3SCB Medical College, Department of Medicine, cuttack, India

Abstract

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.

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