Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children

Abstract

Ficolins are pattern-recognition molecules that appear to be relevant for innate immune defence against infections. The ficolin genes in Caucasians are polymorphic and genetic variations may have functional consequences, both in relation to function and concentration. Low levels of Ficolin-2 have been suggested to associate with recurrent respiratory tract infections (RTI), whereas data on Ficolin-3 are still very limited. We investigated the association between variation in genes encoding Ficolin-2 (FCN2) and Ficolin-3 (FCN3) and frequency of RTI during the first 4 years of life. The study population consisted of 900 children from a large, population-based birth cohort of Dutch children, followed prospectively from birth to 4 years of age. The number of RTI was assessed by annual parental questionnaires. Nine single nucleotide polymorphisms in FCN2 and two in FCN3, all based on functionality or haplotype-tagging characteristics, were determined and haplotypes constructed. We found that single nucleotide polymorphisms in FCN2 and FCN3 were not associated with increased risk of RTI during the first 4 years of life. No difference existed between haplotype-frequencies of FCN2 and FCN3 in children grouped according to the reported number of RTI. In conclusion, at a population level, genetic variation in ficolin genes FCN2 and FCN3 do not seem to contribute to the risk of RTI in Caucasian children.

Fig. 1

Schematic representation of single nucleotide polymorphisms (SNPs) and haplotypes studied of the Ficolin-2 (FCN2) gene.

Fig. 2

Schematic representation of single nucleotide polymorphisms (SNPs) and haplotypes studied of the Ficolin-3 (FCN3) gene.

Fig. 3

Percentage of children according to annual reported frequency of respiratory tract infections (RTI) (0, 1–2, ≥ 3) as derived from questionnaires in years 1, 2, 3 and 4 and stratified for estimated Ficolin-2 (FCN2) haplotype. Only children homozygous for haplotypes with estimated frequency > 5% are included in this analysis. The haplotypes are constructed from the five functionally relevant polymorphisms in FCN2: −986A > G, −602G > A, −4A > G, Thr236Met and Ala258Ser.