MASP1 Gene Polymorphism and MASP-3 Serum Levels in Patients with Chronic Chagas Disease

Immunol Invest. 2022 Oct;51(7):2108-2121. doi: 10.1080/08820139.2022.2110503. Epub 2022 Sep 27.

Abstract

Introduction: Chagas disease (CD), caused by Trypanosoma cruzi, is a major public health issue worldwide affecting 6-7 million people, mainly in Latin America. The complement system plays a crucial role in host immune defense against T. cruzi infection and during the chronic phase of CD; however, the role of the MBL-associated serine protease 1 (MASP1) gene encoding MASP-1, MASP-3, and MAp44 complement proteins has not yet been reported in CD. This study investigated the possible association between MASP1 gene polymorphisms and MASP-3 protein serum levels in chronic CD and its clinical forms.

Methods: Five polymorphisms of MASP1 gene regulatory regions were genotyped in 214 patients with CD and 197 healthy controls (rs7609662 G>A, rs13064994 C>T, rs72549262 C>G, rs1109452 C>T and rs850314 G>A). MASP-3 serum levels were assessed in 70 patients and 66 healthy controls. Clinical data, serum levels of complement proteins (ficolin-2, ficolin-3 and MBL) and inflammatory markers (pentraxin-3 and hsCRP) were also included in the analyses.

Results: A significant association of the MASP1 GC_CCA haplotype with CD (padj= 0.002; OR 3.17 [1.19-8.39]) and chronic chagasic cardiomyopathy (CCC) (padj= 0.013; OR 4.57 [1.37-15.16] was observed. MASP-3 and pentraxin-3 levels were positively correlated in the patients (rho = 0.62; p = 0.0001). MASP-3 levels were not associated with MASP1 polymorphisms or CD and its clinical forms. Furthermore, no correlation was observed between MASP-3 levels and that of ficolin-2, ficolin-3, MBL and hsCRP.

Conclusion: Our findings suggest a possible role for the MASP1 GC_CCA haplotype in susceptibility to chronic CD and CCC clinical forms.

Keywords: Chagas disease; MASP-3; MASP1; complement.

MeSH terms

  • C-Reactive Protein
  • Chagas Disease* / genetics
  • Complement System Proteins
  • Humans
  • Mannose-Binding Protein-Associated Serine Proteases* / genetics
  • Mannose-Binding Protein-Associated Serine Proteases* / metabolism
  • Polymorphism, Genetic

Substances

  • Complement System Proteins
  • C-Reactive Protein
  • MASP1 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases