Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease.

Abstract MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF ( P  = 0.02, OR = 0.36) and RHD ( P  = 0.01, OR = 0.25). In contrast, haplotypes that share the intron 9 – exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD ( P  = 0.02, OR = 4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients ( P MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.