Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

PLoS One. 2015 Nov 23;10(11):e0141847. doi: 10.1371/journal.pone.0141847. eCollection 2015.

Abstract

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Chagas Cardiomyopathy / genetics*
  • Chagas Cardiomyopathy / physiopathology
  • Chagas Disease / genetics*
  • Chagas Disease / physiopathology
  • Chronic Disease
  • Digestive System Diseases / genetics*
  • Female
  • Gene Frequency / genetics
  • Genes, Dominant
  • Genetic Predisposition to Disease*
  • Heart Ventricles / physiopathology
  • Humans
  • Inheritance Patterns / genetics
  • Male
  • Middle Aged
  • Models, Genetic
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, CCR5 / genetics*
  • Systole

Substances

  • CCR5 protein, human
  • Receptors, CCR5

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo [FAPESP grant numbers #2011/08075-4 to LCM; #2011/19439-7 to AVSC; #2012/20735-2 to AVSC; #2012/05580-2 to CRB]; Brazilian Ministry of Education Scholarship – Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (to APO; AVSC; CRB) and Institutional Research Grant BAP-FAMERP to LC. The opinions, assumptions, and conclusions or recommendations expressed in this material are the responsibility of the authors and do not necessarily reflect the views of FAPESP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.