Variant mannose-binding lectin 2 genotype is a risk factor for reactive systemic amyloidosis in rheumatoid arthritis

Objective. The aim of this study was to investigate whether polymorphism of the mannose-binding lectin 2 (MBL2) gene is related to the occurrence of systemic AA amyloidosis in patients with rheumatoid arthritis (RA). Methods. MBL2 structural gene polymorphisms at codon 52 (CGT -> TGT, Arg -> Cys; D), codon 54 (GGC -> GAC, Gly -> Asp; B) and codon 57 (GGA -> GAA, Gly -> Glu; C), and MBL2 promoter region polymorphism at position -221 (G -> C) were examined in 57 patients with RA complicated by biopsy-proven reactive amyloidosis and 51 control RA patients without amyloid. Results. A strong association was found between the presence of a structural MBL2 gene variant O (B, D or C) and the occurrence of amyloidosis in RA patients: 29 of 57 (50.9%) of the RA patients with amyloid had a variant allele compared with 12 of 51 (23.5%) of the RA patients without amyloid (OR 3.37, 95% CI 1.47-7.72; P = 0.004). Conclusion. We conclude that variant MBL2 structural genotype constitutes a significant risk factor for reactive amyloidosis in RA and that the increased risk is probably related to MBL-mediated impairment of mononuclear phagocyte function.