Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease.
Ficolins are pattern-recognition proteins involved in innate immunity, which upon binding to their specific pathogen-associated molecular patterns on the microbial surfaces trigger the immune response either by binding to collectin cellular receptors or by initiating the complement lectin pathway. In humans, three ficolin genes have been identified, which encode ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen). Ficolin-2 was shown to bind to lipoteichoic acid, a cell wall constituent in all Gram-positive bacteria such as Streptococcus pyogenes, which is the aetiological agent of rheumatic fever (RF) and its most severe sequelae, chronic rheumatic heart disease (CRHD). Here we investigated polymorphisms in the promoter region of the FCN2 gene (at positions -986/-602 and +4) in 122 patients with RF and CRHD and in 210 healthy subjects from the same geographic region and socioeconomic background. The haplotype -986/-602/-4 G/G/A, which is related to low levels of L-ficolin, was observed more frequently in the CRHD group when compared to the healthy subjects [99/162, 61.1% versus 211/420, 50.2%, odds ratio (OR) 1.6, confidence interval (CI) 95% 1.1-2.3, P = 0.021]. The haplotype -986/-602/-4 A/G/A was observed more frequently in the healthy group when compared to the affected (RF plus CRHD) subjects (31/420, 7.4% versus 6/244, 2.5%, OR 3.2, CI 95% 0.13-0.77, P = 0.008). Based on those findings, one can conclude that polymorphisms associated with low levels of L-ficolin level may predispose an individual to recurrent and/or more severe streptococcal infection.
Messias-Reason
I J
IJ
Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany.
Schafranski
M D
MD
Kremsner
P G
PG
Kun
J F J
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012213:Rheumatic Fever / Q000235:genetics*; D012214:Rheumatic Heart Disease / Q000235:genetics; D012306:Risk; D013290:Streptococcal Infections / Q000235:genetics*; D055815:Young Adult; D000097604:Ficolins
D037102:Lectins; D000097604:Ficolins