Association of ficolin-2 (FCN2) functional polymorphisms and protein levels with rheumatic fever and rheumatic heart disease: relationship with cardiac function.

Background: A role for ficolin (FCN) 2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested. The aim of the study was to evaluate a possible relationship between single nucleotide polymorphisms located at positions -602 and -4 of the FCN2 gene and FCN2 serum levels and risk of development of rheumatic fever (RF) and rheumatic heart disease (RHD).

Methods: Seventy-seven Caucasian Egyptian patients with RF were recruited with a control group of 43 healthy subjects. DNA was extracted for analysis of the FCN2 gene at positions -602 and -4 and serum protein level was measured by ELISA.

Results: FCN2 AA genotype at the -4 position was more frequently observed in RF and RHD patients, as compared to healthy subjects (p = 0.005 and p = 0.013, respectively); furthermore, the A allele was identified as a possible risk factor for the development of RF (p = 0.023, OR = 1.852, 95% CI: 1.085-3.159). The haplotype -602/-4 G/A, which was associated with low median levels of L-ficolin, was observed more frequently in the RF group when compared to the healthy subjects (74/162, 48.1% vs. 29/420, 33.7%, OR = 1.834, 95% CI: 1.034-3.252, p = 0.038). Low serum ficolin-2 level was associated with ESV and EDV increases. FCN 2 level was significantly lower with AA genotypes than GG+AG genotypes of the -4 position (56.68 ±17.90 vs. 66.05 ±18.79, p = 0.008).

Conclusions: Polymorphisms linked to low levels of L-ficolin may render an individual at risk of recurrent and/or severe streptococcal infection. The -4 AA genotype and -602/-4 G/A haplotype are possible risk factors for the development of carditis.