Association of toll-like receptors polymorphisms with atopy and asthma symptoms in Latin American children.

BACKGROUND

Polymorphisms in TLRs genes have been implicated in the physiopathological mechanisms of atopy and asthma.

OBJECTIVE

The aim of this study was to assess the association between polymorphisms on TLRs and atopy/asthma in a highly admixture population of children from Salvador, Bahia, Brazil.

METHODS

Cross-sectional study. We analyzed 192 SNPs in TLRs genes (TLR1-TLR9) in 1187 children aged 4-11 years living in the urban periphery of Brazil. Bivariate analyses were performed to evaluate the association between TLRs SNPs and asthma syptoms, skin prick test (SPT), and specific IgE to aeroallergens (sIgE). In addition, polytomous logistic regression was used to assess the association between TLRs SNPs and asthma phenotypes, adjusting for sex, age, helminth infection and individual ancestry. Lastly, logistic regression was used to assess gene-environment interactions between TLRs SNPs and different infections in the risk of asthma and atopy.

RESULTS

For SPT positivity the most significant associations were identified for rs4833095 in in TLR1 (OR: 1.42; 95 % CI: 1.17-1.71; p = 0.00002) and rs1039559 in TLR6 (OR: 1.40; CI: 1.15-1.70; p = 0.0009). For sIgE to aeroallergens significant associations were observed for rs5743810 in TLR6 (OR: 1.43; 95 % CI: 1.13-1.81 p = 0.004), rs3853839 in TLR7 (OR: 1.38; 95 % CI: 1.08-1.76; p = 0.009), and the rs5744139 was the most significantly associated in TLR5 gene (OR: 2.0, 95 % CI: 1.17-3.41; p = 0.007). For asthma symptoms significant positive associations were observed for the rs4833095 in TLR1 (OR: 1.32; 95 % CI: 1.07-1.62; p = 0.009) and rs2241097 in TLR5 (OR: 1.36; 95 % CI: 1.08-1.73; p = 0.009). Furthermore, rs4833095 (OR: 1.38, 95 % CI: 1.03-1.83; p = 0.028) in TLR1 and rs2241097 (OR: 1.45; 95 % CI: 1.06-2.00; p = 0.020) in TLR5 were positively associated with non-atopic asthma, while rs1039559 (OR: 1.45; 95 % CI: 1.06-2.00; p = 0.036) and rs6531673 (OR: 1.48; 95 % IC: 1.08-2.02; p = 0.014) in TLR6 were associated with increased risk for atopic asthma. Gene-environment interaction analyses further revealed that specific infections (e.g., Toxoplasma gondii, HSV, H. pylori, HAV, EBV, and helminths) significantly modified these associations.

CONCLUSION

The results suggest functional significance of polymorphisms on TLR1 subfamily, TLR5 and TLR6 on atopy and asthma, as well as pathogens involved in gene-environment interaction could also play a role in the immunopathological mechanism of atopy and asthma in the studied population.