TLR4 Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

Johanna T Teräsjärvi,Laura Toivonen,Juho Vuononvirta,Ville Peltola,Jussi Mertsola,Qiushui He

doi:10.3390/genes11070768

Abstract

We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. TLR4 polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between TLR4 genotype, bacterial colonization, and asthma were analyzed. Children with TLR4 AG or GG genotype were more often colonized with Moraxella catarrhalis at 2 months of age (p = 0.009) and Haemophilus influenzae at 13 months of age (p = 0.018). Children who were colonized with H. influenzae at 13 months of age had a significantly higher risk of later development of asthma (p = 0.004). M. catarrhalis or H. Influenzae colonization at 2 months of age or TLR4 genotype Asp299Gly were not associated with the development of childhood asthma. TLR4 Asp299Gly polymorphism was associated with an increased risk of colonization of M. catarrhalis and H. influenzae in children. The colonization with H. influenzae at 13 months of age was associated with a higher risk of later development of childhood asthma.

Highlights

After birth, neonates are rapidly colonized with a variety of microbes
It was found that TLR4 polymorphism was associated with increased risk for colonization by of age was found in children with a variant type of TLR4 than in those with wild type
In this prospective cohort study, we show that TLR4 Asp299Gly polymorphism can markedly increase the risk of colonization with two Gram-negative bacteria, H. influenzae and M. catarrhalis

Summary

Introduction

Neonates are rapidly colonized with a variety of microbes. The nasopharyngeal (NP)microbiota is highly dynamic over the first years of life [1]. Neonates are rapidly colonized with a variety of microbes. Some of the NP microbes are potential pathogens, such as Haemophilus influenzae and Moraxella catarrhalis. These bacteria are associated with susceptibility to respiratory tract infections and increased risk for the later development of asthma, which is the most common chronic disease in children [2,3]. Around 10–20% of children suffer asthma-like symptoms at least once in the childhood, and 4–7% will have pediatric asthma [4,5]. Genetic alterations in the pathogen recognition system of innate immunity may increase risk for recurrent respiratory infections and atopy, which may further cause a predisposition for the

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