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

Abstract

SummaryFicolins 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.

New Insights into the Role of Ficolins in the Lectin Pathway of Innate Immunity

“…Furthermore, in renal transplantation, this SNP in the donor predicts improved outcome with lower incidence of severe rejection (Eikmans et al, 2012). In contrast, it was reported that three promoter SNPs (-986, -602, and -4) and two nonsynonymous SNPs (Thr236Met and Ala258Ser) are not associated with invasive pneumococcal disease (Chapman et al, 2007), respiratory tract infection (Ruskamp et al, 2009), or Behcet's disease (Chen et al, 2006).…”

The Lack of Association between <b><i>FCN2</i></b> Gene Promoter Region Polymorphisms and Dental Caries in Polish Children

“…A lack of association of those FCN2 polymorphisms with other infectious diseases was demonstrated in other studies, that is with respiratory tract infections [Ruskamp et al, 2009], invasive pneumococcal disease [Chapman et al, 2007], pulmonary tuberculosis [Xu et al, 2015] or visceral leishmaniasis [Mishra et al, 2015].…”

“…Several studies investigated the association of FCN2 functional polymorphisms and/or ficolin-2 serum levels with different infectious diseases, including respiratory infections [Atkinson et al, 2004;Ruskamp et al, 2009], pneumonia [Chalmers et al, 2014], invasive pneumococcal disease [Chapman et al, 2007], pulmonary tuberculosis [Luo et al, 2013;Xu et al, 2015], leprosy [de MessiasReason et al, 2009;Zhang et al, 2013], hepatitis B [Hoang et al, 2011;Chen et al, 2015], leishmaniasis [Assaf et al, 2012;Mishra et al, 2015], schistosomiasis [Ouf et al, 2012] or autoimmune diseases with bacterial involvement, such as rheumatic fever and chronic rheumatic heart disease .…”

The Genetics of Ficolins

“…The observed SNPs are likely to cause specific alterations of the FBG domain, thus affecting the binding to ligands, but they are not located in the observed FBG binding sites that have been deduced based on crystallographic observations [44] . Two well-conducted studies have explored the putative importance of the FCN2 polymorphisms and the possible importance in invasive pneumococcal disease in adults and self reported respiratory infections in children [65,68] , but no significant associations were observed. Rheumatic fever and chronic rheumatic heart disease has been investigated for association with promoter polymorphisms in the FCN2 gene [69] .…”