MBL2 and FCN2 gene polymorphisms in a cohort of Italian children with rheumatic fever: A case-control study

Semin Arthritis Rheum. 2017 Oct;47(2):264-268. doi: 10.1016/j.semarthrit.2017.04.006. Epub 2017 Apr 27.


Background: Mannose-binding lectins and human ficolins are pattern-recognition proteins involved in innate immunity. A role for MBL2 and FCN2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested.

Objectives: The aim of this study is to evaluate the presence of MBL2 and FCN2 gene polymorphisms (SNPs) in children with a history of rheumatic fever (RF) and to investigate their possible role in RF clinical presentation and disease course.

Methods: A total of 50 Caucasian patients with RF were recruited with a control group of 52 healthy children. DNA was extracted for analysis of MBL2 gene (exon 1, codons: 52, 54, and 57) and FCN2 gene (promoter region at position -986, -602, and -4).

Results: The FCN2 AG genotype at the -986 position was more frequently observed in patients, as compared to healthy subjects (p = 0.006); furthermore, the A allele was identified as a possible risk factor for the development of RF (OR = 7.14, CI: 2.439-20.89). Conversely, the GG genotype at the same position was observed more frequently in the control group and can be considered a protective factor for the development of the disease (p = 0.001, OR = 8.37, 95% CI: 2.763-25.33). In addition, the FCN2 GG and AG genotypes in the -4 position were also found to be protective factors for the development of RF and for carditis respectively (OR = 3.32, CI: 1.066-10.364; OR = 0.15, 95% CI: 0.037-0.566). Finally, the AA genotype in the -602 position was associated with a late onset of RF (p = 0.006). The analysis of the MBL2 gene only resulted in a higher frequency of the AA genotype on position 57 in controls as compared to patients (p = 0.025).

Conclusions: This is the first study evaluating the FCN2 gene polymorphisms in patients with RF and rheumatic carditis finding a protective effect of -986 GG and -4 GG genotypes in the development of RF and the -4 AG genotype for the development of carditis. Our data do not support a possible role for MBL2 polymorphisms in the pathogenesis and in the clinical manifestations of RF.

Keywords: Children; Ficolin; Gene polymorphisms; Mannose-binding lectin; Rheumatic fever; SNPs.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Ficolins
  • Genotype
  • Humans
  • Italy
  • Lectins / genetics*
  • Male
  • Mannose-Binding Lectin / genetics*
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Rheumatic Fever / genetics*


  • Lectins
  • MBL2 protein, human
  • Mannose-Binding Lectin