MASP2 haplotypes are associated with high risk of cardiomyopathy in chronic Chagas disease

Mannose-binding lectin (MBL) initiates complement on Trypanosoma cruzi through the MBL-associated serine protease 2 (MASP2). We haplotyped six MASP2 polymorphisms in 208 chronic chagasic patients, being 81 indeterminate and 123 symptomatic (76 with cardiac, 19 with digestive and 28 with cardiodigestive forms) and 300 healthy individuals from Southern Brazil, using PCR with sequence-specific primers. The g.1961795C, p.371D diplotype (short CD) occurred at a higher frequency among symptomatic patients, compared with the indeterminate group (PBf = 0.012, OR = 3.11), as well as genotypes with CD, but not with the g.1945560A in the promoter in cardiac patients (PBf = 0.012, OR = 13.54). CD haplotypes linked to the p.P126L and p.V377A variants were associated with reduced MASP-2 levels (P < 0.0001) but not reduced MBL/MASP-2/C4 complexes. MASP2*CD genotypes, most of them generating low MASP-2 levels, are associated with high risk of chagasic cardiomyopathy. Rapid MASP2 genotyping might be used to predict the risk of symptomatic disease.

► First study with MASP2 polymorphisms and MASP-2 levels in chronic Chagas disease. ► First disease association study to investigate MASP2 known-phase haplotypes. ► Genotypes with CD (not with g.1945560A) predispose to cardiac disease (OR = 13.54). ► CD is associated with low MASP-2 levels, but not lower complement activation. ► MASP2*CD may be a potential marker of progression to symptomatic Chagas disease.