RESUMO
INTRODUCTION: Chagas disease (CD) is an important public health problem in Brazil and worldwide. Aging and obesity are important matters in patients with CD, as is hypovitaminosis D3, which can decrease the quality of life of these patients. Immunomodulation mediated by vitamin D3, especially the production of antimicrobial peptides such as cathelicidin LL-37, might be related to the severity and symptoms of CD. This study aimed to determine the serum levels of vitamin D and LL-37 and VDR gene polymorphisms in patients with chronic CD. METHODS: This study included male patients with cardiac and indeterminate clinical forms of CD. Clinical, anthropometric, and blood parameters were obtained. Serum levels of 25(OH)D3 and LL-37 were determined by chemiluminescence and enzyme-linked immunosorbent assay respectively. Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) polymorphisms of the VDR gene were investigated by PCR-RFLP. RESULTS: Sixty-four patients were included in the study: 18 of the cardiac form and 46 of the indeterminate form. No differences in age, ethnicity, BMI, arterial hypertension, diabetes mellitus, or dyslipidemias were observed between groups. However, the serum levels of 25(OH)D3, but not of LL-37, were lower in the cardiac form group. The association among polymorphisms, vitamin D, and clinical form was not significant. CONCLUSIONS: Decreased levels of vitamin D suggest an association with the cardiac form of CD. Studies investigating the roles of vitamin D and LL-37 in the immune response and their associations with VDR polymorphisms and disease susceptibility are necessary.
Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Doença de Chagas/sangue , Doença de Chagas/genética , Colecalciferol/sangue , Polimorfismo Genético/genética , Receptores de Calcitriol/genética , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade , CatelicidinasRESUMO
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), although discovered more than a century ago, is still a not very well-elucidated aspect. Individuals in the chronic phase of the disease may present asymptomatic clinical form or symptomatologies related to the cardiac, digestive systems, or both (mixed clinical form). SNPs (single nucleotide polymorphisms) have been identified as important markers because they constitute about 90% of the variation in the human genome. One of them is localized to the ACAT-1 gene (cholesterol acyltransferase 1) (rs1044925) and has been linked to lipid disorders. Some studies have suggested the interaction between T. cruzi and the lipid metabolism of the host. Therefore, the objective of the present study was to evaluate the association between the ACAT-1 gene rs1044925 SNP in relation to clinical manifestations in patients with chronic Chagas disease. A total of 135 individuals with chronic Chagas disease, 86 (63.7%) asymptomatic individuals and 49 (36.3%) symptomatic patients (22 with cardiac clinical form, 18 with digestive form and 9 with mixed form) participated in the study. To evaluate the polymorphism, the PCR-RFLP technique were used. There was a significant difference and a higher frequency of AA and AC genotypes (p = 0.047 and p = 0.016, respectively) of the ACAT-1 gene in asymptomatic chagasic individuals. The result suggests a protective character of the AA and AC genotypes of the rs1044925 SNP in relation to the presence of symptomatic clinical manifestations of the disease in chronic chagasic individuals.
Assuntos
Doença de Chagas/genética , Polimorfismo de Nucleotídeo Único , Esterol O-Aciltransferase/genética , Idoso , Doenças Assintomáticas , Doença de Chagas/parasitologia , Doença Crônica , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Trypanosoma cruzi/fisiologiaRESUMO
Abstract INTRODUCTION: Chagas disease (CD) is an important public health problem in Brazil and worldwide. Aging and obesity are important matters in patients with CD, as is hypovitaminosis D3, which can decrease the quality of life of these patients. Immunomodulation mediated by vitamin D3, especially the production of antimicrobial peptides such as cathelicidin LL-37, might be related to the severity and symptoms of CD. This study aimed to determine the serum levels of vitamin D and LL-37 and VDR gene polymorphisms in patients with chronic CD. METHODS: This study included male patients with cardiac and indeterminate clinical forms of CD. Clinical, anthropometric, and blood parameters were obtained. Serum levels of 25(OH)D3 and LL-37 were determined by chemiluminescence and enzyme-linked immunosorbent assay respectively. Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) polymorphisms of the VDR gene were investigated by PCR-RFLP. RESULTS: Sixty-four patients were included in the study: 18 of the cardiac form and 46 of the indeterminate form. No differences in age, ethnicity, BMI, arterial hypertension, diabetes mellitus, or dyslipidemias were observed between groups. However, the serum levels of 25(OH)D3, but not of LL-37, were lower in the cardiac form group. The association among polymorphisms, vitamin D, and clinical form was not significant. CONCLUSIONS: Decreased levels of vitamin D suggest an association with the cardiac form of CD. Studies investigating the roles of vitamin D and LL-37 in the immune response and their associations with VDR polymorphisms and disease susceptibility are necessary.
Assuntos
Humanos , Masculino , Polimorfismo Genético/genética , Doença de Chagas/genética , Doença de Chagas/sangue , Receptores de Calcitriol/genética , Colecalciferol/sangue , Peptídeos Catiônicos Antimicrobianos/sangue , Biomarcadores/sangue , Pessoa de Meia-IdadeRESUMO
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), although discovered more than a century ago, is still a not very well-elucidated aspect. Individuals in the chronic phase of the disease may present asymptomatic clinical form or symptomatologies related to the cardiac, digestive systems, or both (mixed clinical form). SNPs (single nucleotide polymorphisms) have been identified as important markers because they constitute about 90% of the variation in the human genome. One of them is localized to the ACAT-1 gene (cholesterol acyltransferase 1) (rs1044925) and has been linked to lipid disorders. Some studies have suggested the interaction between T. cruzi and the lipid metabolism of the host. Therefore, the objective of the present study was to evaluate the association between the ACAT-1 gene rs1044925 SNP in relation to clinical manifestations in patients with chronic Chagas disease. A total of 135 individuals with chronic Chagas disease, 86 (63.7%) asymptomatic individuals and 49 (36.3%) symptomatic patients (22 with cardiac clinical form, 18 with digestive form and 9 with mixed form) participated in the study. To evaluate the polymorphism, the PCR-RFLP technique were used. There was a significant difference and a higher frequency of AA and AC genotypes (p = 0.047 and p = 0.016, respectively) of the ACAT-1 gene in asymptomatic chagasic individuals. The result suggests a protective character of the AA and AC genotypes of the rs1044925 SNP in relation to the presence of symptomatic clinical manifestations of the disease in chronic chagasic individuals(AU).