Ficolin‐1 gene (FCN1) −144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under‐five Egyptian children: A multicenter study

Abstract

Background Pneumonia is the foremost cause of child death worldwide. M‐ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. Objectives To investigate the FCN1 −144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under‐five Egyptian children. Methods This was a prospective multicenter study that included 620 children hospitalized with World Health Organization‐defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR‐SSP, while serum M‐ficolin levels were assessed by ELISA. Results The FCN1 A/A genotype and A allele at the −144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18‐2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19‐1.65]; for the A allele); P < .01. The FCN1 −144 A/A homozygous patients had significantly higher serum M‐ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 −144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96‐10.25]; P = .01). Conclusion The FCN1 A/A genotype at the −144 position was associated with high M‐ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under‐five Egyptian children.

Effect of Polymorphisms in the FCN1, FCN2, and FCN3 Genes on the Susceptibility to Develop Rheumatoid Arthritis: A Systematic Review

“…In addition, the rs7851696 variant in the FCN2 gene has been associated with delayed graft function and acute graft rejection in renal transplant patients (T allele = OR 1.71; 95% CI: 1.02-2.87, p value = 0.048) [ 22 ]; in other diseases such as vasculitis, ficolin-M expression is elevated in peripheral blood mononuclear cells and inflamed areas [ 23 ] and severe pneumonia in the Egyptian population [ 24 ].…”

FCN1 polymorphisms are not the markers of dental caries susceptibility in Polish children: A case‐control study

“…Variants of FCN1 gene and/or serum/plasma levels of ficolin‐1 were examined only in quite a few diseases (or pathological states) associated with autoimmunity such as rheumatoid arthritis [Vander Cruyssen et al., 2007], systemic lupus erythematosus [Addobbati et al., 2016], rheumatic fever and rheumatic heart disease [Catarino et al., 2018], type 1 diabetes mellitus [Anjosa et al., 2016], systemic inflammation [Munthe‐Fog et al., 2012], but also in some infectious diseases [Ren et al., 2014], such as leprosy [Boldt et al., 2013], pneumococcal disease [Kjaer et al., 2013], severe pneumonia [Elkoumi et al., 2020], as well as in sepsis [Świerzko et al., 2016]. It has been shown that plasma concentrations of ficolins may reflect the course of infection [Sokołowska et al., 2020; Świerzko et al., 2016; Świerzko et al., 2020].…”

“…Analysis of another DMFT cut-off value, that is, DMFT =1, also revealed lack of significant differences in FCN1 genotype, allele, and haplotype frequencies between cases (children with DMFT ≥1) and controls (children free from caries, with DMFT =0) (results not shown). associated with autoimmunity such as rheumatoid arthritis [Vander Cruyssen et al, 2007], systemic lupus erythematosus [Addobbati et al, 2016], rheumatic fever and rheumatic heart disease [Catarino et al, 2018], type 1 diabetes mellitus [Anjosa et al, 2016], systemic inflammation [Munthe-Fog et al, 2012], but also in some infectious diseases [Ren et al, 2014], such as leprosy [Boldt et al, 2013], pneumococcal disease [Kjaer et al, 2013], severe pneumonia [Elkoumi et al, 2020], as well as in sepsis [Świerzko et al, 2016]. It has been…”

How could we forget immunometabolism in SARS-CoV2 infection or COVID-19?

“…The myeloid cell compartment in the lungs of severe COVID-19 patients show an increased number of neutrophils, ficolin-1 (FCN1) þ monocytes, secreted phosphoprotein 1 (SPP1) þ monocyte-derived macrophages, and CD14 þ CD16 þ (Figure 2A and B) [26,29]. The FCN1 is a recognition molecule of the lectin complement pathway, and the high FCN1 level is associated with the severe inflammation during pneumonia [76,77]. Neutrophils infiltrated in the lungs of the severe COVID-19 patients are crucial innate immune cell generating broad type 1 IFN response, with a lesser extent to FCN1 þ monocytes ( Figure 2B) [29].…”