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

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 (p_adj= 0.002; OR 3.17 [1.19–8.39]) and chronic chagasic cardiomyopathy (CCC) (p_adj= 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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Chagas disease
• complement
• MASP1
• MASP-3

Acknowledgments

The authors wish to thank Fundação Araucária (Programa Pesquisa para o Sistema Único em Saúde – PPSUS Fundação Araucária-PR/SESA-PR/CNPq/MS-Decit), Coordenação de Aperfeiçoamento de pessoal de Nível Superior (CAPES),Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and PROBRAL program (88887.371430/2019-00) a partnership between CAPES and German Academic Exchange Service (Deutscher Akademischer Austauschdienst - DAAD).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data included in this article will be shared upon reasonable request to the corresponding author.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2022.2110503

Additional information

Funding

This work was supported by grants and scholarships from Fundação Araucária (Programa Pesquisa para o Sistema Único em Saúde – PPSUS Fundação Araucária-PR/SESA-PR/CNPq/MS-Decit), Coordenação de Aperfeiçoamento de pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and PROBRAL program (88887.371430/2019-00).