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270 Association of tlr2 (23bp ins/del) polymorphism with systemic lupus erythematosus (sle) and p. falciparum malaria: a study in malaria endemic area of odisha, india
  1. B Das1,
  2. R Tripathy2,
  3. S Pattanaik1 and
  4. A Panda3
  1. 1S.C.B. Medical College, Medicine, Cuttack, India
  2. 2S.C.B. Medical College, Biochemistry, Cuttack, India
  3. 3Central University of Jharkhand, Centre for Life Sciences, Ranchi, India

Abstract

Background and aims Human toll-like receptors (TLRs) participate in the innate response and signal the activation of adaptive immunity. TLRs play a vital role in sensing infection. A common 23 bp insertion/deletion polymorphism at 5’UTR of TLR2 gene has been shown to affect TLR2 expression and plasma levels of pro-inflammatory molecules. We hypothesised that a mutation at 5’UTR region of TLR2 gene could be associated with susceptibility/resistance to SLE and malaria. We performed a hospital based case-control study on SLE patients residing in P. falciparum endemic areas.

Methods Two hundred female SLE patients and age and sex, matched healthy controls were enrolled. 120 P. falciparum infected patients including 50 uncomplicated cases and 70 severe malarial patients were included.. TLR2 (23bp ins/del) polymorphism was typed by polymerase chain reaction (PCR). 20% samples were randomly sequenced for validation of PCR results.

Results The mean age and disease duration of SLE patients were 27.44 and 2.91 years respectively. Prevalence of mutants (ins/del+del/del) of TLR2 gene polymorphism were significantly lower in SLE patients compared to healthy controls (p=0.02; OR=0.54). Distribution of TLR2 variants were comparable among different clinical phenotypes of SLE. The TLR2 5’UTR mutants were associated with elevated TNF alpha, IL1 beta and IL6 compared to the wild genotypes. Mutants were more prevalent in severe malaria patients than uncomplicated cases (p=0.05; OR=2.31).

Conclusions TLR2 5’UTR 23bp ins/del variants are associated with development of severe disease in P. falciparum malaria but possibly an evolutionary mechanism to protect SLE patients against severe malaria in endemic areas

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