Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis

Abstract

Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0.03). The adjusted odds ratio (aOR) was 4.30 (95% CI 1.30–14.29). Asthma ever was more common (34.6%) in girls with the TLR7 variant AT or TT genotype versus those who were homozygous for the major allele A (12.5%) (p = 0.03). The adjusted OR was 3.93 (95% CI 1.06–14.58). Corresponding associations were not seen in boys. There were no significant associations between TLR3, TLR4, TLR8, or TLR9 polymorphisms and post-bronchiolitis asthma. Polymorphism in the TLR10 gene increases and in the TLR7 gene may increase the risk of asthma in preschool-aged children after infant bronchiolitis.

Toll‐like receptor 1 and 10 gene polymorphisms are linked to postbronchiolitis asthma in adolescence

“…Earlier follow‐up studies in this prospective postbronchiolitis cohort documented the association between TLR1 rs5743618 polymorphism and asthma at one to six years of age , and the association between TLR10 rs4129009 polymorphism and asthma at five to seven years of age . There have not been any other previous studies with regard to TLR1 rs5743618 and asthma.…”

“…We have prospectively followed 166 Finnish children as they were hospitalised for bronchiolitis when they were less than six months of age and by the age of 11–13, 138 children were still taking part in the study. Our explanatory studies of the polymorphisms of all 10 TLR genes in this cohort showed that TLR1 rs5743618 polymorphism was associated with asthma at one to six years of age and TLR10 rs4129009 polymorphism was associated with asthma at five to seven years of age . In both polymorphisms, the variant genotype, including the minor allele, was associated with a greater asthma risk.…”

“…There have not been any other previous studies with regard to TLR1 rs5743618 and asthma. In fact, we evaluated all 10 TLRs that have been identified to date in these previous exploratory studies , but the rest of them did not show any associations with postbronchiolitis asthma at any age. Therefore, we just included TLR1 rs5743618 and TLR10 rs4129009 polymorphisms in this confirmatory study at 11–13 years of age.…”

“…Polymorphisms of the TLR1 rs5743618 (1805 G>T) and TLR10 rs4129009 (2322 A>G) genes were respectively determined by the National Institute of Health and Welfare, Turku ( TLR1 ), and the Department of Medical Microbiology and Immunology, University of Turku ( TLR10 ), Finland, as previously described . These single nucleotide polymorphisms were selected due to their previously reported functional properties and the previous exploratory findings from this cohort .…”

Disease severity in respiratory syncytial virus infection: Role of host genetic variation

“…Lauhkonen et al found that TLR7 rs179008 SNP has some exploratory associations with postbronchiolitis lung function deficiency . This variation may increase the risk of asthma in preschool‐aged children after infant bronchiolitis with 70.5% frequency of RSV infection . Another group, through genotyping of 19 polymorphisms in the autosomal TLRs, found weak association of one TLR9 promoter polymorphism (rs5743836) and TLR10 haplotypes with RSV infection .…”