title: Association of mannose-binding lectin gene polymorphism but not of mannose-binding serine protease 2 with chronic severe aortic regurgitation of rheumatic etiology.
abstract: N-Acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Antistreptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by the MBL2 gene, a soluble pathogen recognition receptor, has high affinity for GlcNAc. We postulated that mutations in exon 1 of the MBL2 gene associated with a deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology. We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of the MBL2 gene at codons 52, 54, and 57 by using a PCR-restriction fragment length polymorphism-based method. We observed a significant difference in the prevalence of defective MBL2 alleles between patients with chronic severe AR and HC. Sixteen percent of patients with chronic severe AR were homozygotes or compound heterozygotes for defective MBL alleles in contrast to 5% for HC (P = 0.0022; odds ratio, 3.5 [95% confidence interval, 1.6 to 7.7]). No association was detected with the variant of the MASP2 gene. Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.
authors.affiliation: Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil. ramasawm@usp.br
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
authors.forename: Guilherme S
authors.initials: GS
authors.lastname: Spina
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Fae
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Renato
authors.initials: R
authors.lastname: Nisihara
authors.forename: Iara Jose
authors.initials: IJ
authors.lastname: Messias Reason
authors.forename: Max
authors.initials: M
authors.lastname: Grinberg
authors.forename: Flavio
authors.initials: F
authors.lastname: Tarasoutchi
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Luiza
authors.initials: L
authors.lastname: Guilherme
mesh_terms: D000328:Adult; D000483:Alleles; D001022:Aortic Valve Insufficiency / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012216:Rheumatic Diseases / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D037601:Mannose-Binding Lectin; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases