infection is an important mediator of ocular disease in Brazil more frequently than reported
from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is
triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify
the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii
pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken
in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies
> 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association
Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5
= 1.2 x 10-4
] between the C allele (frequency = 0.424;
odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil.
This supports the hypothesis that direct interaction between T. gondii
and TLR9 may trigger proinflammatory responses
that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.