Abstract
The aim of our study was to evaluate whether gene polymorphisms in Toll-like receptors (TLR) constituting TLR2 subfamily are associated with the development of osteitis after Bacillus Calmette-Guerin (BCG) vaccination as newborn.
Methods. Blood samples of 132 former BCG osteitis patients now aged 21-49 years were analyzed in a controlled setting for TLR1 T1805G (rs5743618), TLR2 G2258A (rs5743708) and TLR6 C745T (rs5743810) gene single nucleotide polymorphisms (SNPs). The frequencies of the SNPs were compared to those of the 318 Finnish healthy controls.
Results.The frequencies of the variant genotypes of TLR2 G2258A (11.4% vs 5.7%, p=0.033) and TLR6 C745T (77.3% vs 61.6%, p=0.001) differed between cases and controls. The TLR2 (aOR 2.154, 95%CI 1.026-4.521) and TLR6 (aOR 1.907, 95%CI 1.183-3.075) variant genotypes were associated with an increased risk of BCG osteitis. The frequency of the TLR1 T1805G variant genotype was 19.7% in cases vs.33.6% in controls (p=0.003). The TLR1 variant genotype was associated with a decreased risk of BCG osteitis (aOR 0.554, 95%CI 0.336-0.911). When different combinations of TLR1, TLR2 and TLR6 wild and variant genotypes were compared with the combination of wild genotypes in all three TLRs, only the combination of TLR1 wild, TLR2 variant and TLR6 variant genotype differed significantly between cases and controls.
Conclusions. These results show that there were significant differences in gene polymorphisms of TLR1, TLR2 and TLR6 between the BCG osteitis patients and controls. These results suggest that these polymorphisms play a role in the development of BCG osteitis in vaccinated newborns.
- © 2014 ERS