Abstract
The recently described family of toll-like receptors (TLRs) is a key player in host immunity by mediating inflammatory reactions against a wide range of pathogens. Mutations and polymorphisms in TLRs have revealed the importance of TLRs in human defence against diseases. TLR-2 is reported to interact with different bacterial structures, including lipoproteins, peptidoglycan and lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive protein, sedimentation and white blood cell counts were studied to evaluate the clinical characteristics of the patients. Genomic DNA was extracted from peripheral blood using a standard column extraction technique. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. The PCR products for the TLR-2 gene were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared with healthy adult controls, the Arg753Arg genotype was significantly decreased in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval (95% CI) 0.0034–0.031, p<0.0001]. Significantly, ARF patients were just 16 times more frequent with Gln allele (OR 15.6, 95% CI 7.87–30.8, p<0.0001). Moreover, evidence for an intensifying effect of the Gln allele was noteworthy when patients with Arg753Gln genotype were compared with healthy controls (OR 97.1, 95% CI 32.5–290, p<0.0001). However, no Arg677Trp polymorphism was detected in either patients or controls. Our data suggest that there is strong evidence for the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at position 753 significantly contributes to the pathogenesis of ARF. These results will allow the construction of a profile of individuals prone to ARF and may assist in developing new therapies.
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Abbreviations
- ARF:
-
Acute rheumatic fever
- RHD:
-
Rheumatic heart disease
- TLR:
-
Toll-like receptor
- PCR:
-
Polymerase chain reaction
- RFLP:
-
Restriction fragment length polymorphism
- ASO:
-
Antistreptolysin O
- CRP:
-
C-reactive protein
- ESR:
-
Erythrocyte sedimentation rate
- WBC:
-
White blood cells count
- NF-κB:
-
Nuclear transcription factor kappa B
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Berdeli, A., Celik, H.A., Özyürek, R. et al. TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children. J Mol Med 83, 535–541 (2005). https://doi.org/10.1007/s00109-005-0677-x
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DOI: https://doi.org/10.1007/s00109-005-0677-x