Toll-like receptor 2 subfamily gene polymorphisms are associated with Bacillus Calmette-Guérin osteitis following newborn vaccination

Aim Toll‐like receptor (TLR) 1, 2, 6 and 10, the TLR2 subfamily, are known to be associated with immunity against tuberculosis. We evaluated whether polymorphisms in genes encoding TLR1, TLR2 and TLR6 were associated with osteitis in infants who received the Bacillus Calmette‐Guérin (BCG) vaccination soon after birth. Methods Blood samples from 132 adults aged 21–49 who had BCG osteitis in early childhood were analysed in a controlled study for TLR1 T1805G (rs5743618), TLR2 G2258A (rs5743708) and TLR6 C745T (rs5743810) gene single nucleotide polymorphisms. Results The frequencies of the variant genotypes differed between the cases and controls: 11.4% versus 5.7% for TLR2 G2258A (p = 0.033) and 77.3% versus 61.6% for TLR6 C745T (p = 0.001). The TLR2 and TLR6 variant genotypes were associated with a higher risk of BCG osteitis, with adjusted odds ratios (aOR) of 2.154 (95%CI 1.026–4.521) and 1.907 (95%CI 1.183–3.075), respectively. The frequency of the TLR1 T1805G variant genotype was 19.7% in the cases and 33.6% in the controls (p = 0.003). The TLR1 variant genotype was associated with a lower risk of BCG osteitis (aOR 0.554, 95%CI 0.336–0.911). Conclusion Gene polymorphisms that regulate the function of the TLR2 subfamily play a role in the development of BCG osteitis in vaccinated infants.