RESUMEN
FOXO3, a member of the Forkhead family of proteins, plays a role in controlling immune response. FOXO3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. In this study, we assessed whether this FOXO3 gene polymorphism is related to susceptibility to infection by Trypanosoma cruzi and/or chronic Chagasic cardiomyopathy. A total of 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and chronic Chagasic cardiomyopathy (n = 401) were genotyped for the FOXO3 rs12212067 using TaqMan allelic discrimination. Our results showed no statistically significantly differences between allelic and genotypic frequencies of rs12212067 in seronegative individuals compared with seropositive individuals. Similarly, we observed no evidence of association when asymptomatic individuals were compared with chronic Chagasic cardiomyopathy patients. Our data suggest that the FOXO3 genetic variant rs12212067 do not play an important role in Chagas disease.
Asunto(s)
Cardiomiopatía Chagásica/epidemiología , Cardiomiopatía Chagásica/inmunología , Enfermedades Endémicas , Proteína Forkhead Box O3/genética , Polimorfismo de Nucleótido Simple , Trypanosoma cruzi/inmunología , Adulto , Alelos , Enfermedades Asintomáticas , Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/patología , Enfermedad Crónica , Colombia/epidemiología , Femenino , Proteína Forkhead Box O3/inmunología , Expresión Génica , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Trypanosoma cruzi/patogenicidadRESUMEN
Human host genetic factors have been suggested to be determinants of the prevalence and clinical forms of Chagas disease. In this regard, IL-17A is believed to control parasitemia and protect against heart disease. In this work, we assessed whether IL17A gene polymorphisms are related to infection and/or development of the cardiac form of Chagas disease by genotyping for five IL17A SNPs (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) in 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n=595), seropositive asymptomatic (n=175) and chronic Chagas cardiomyopathy (n=401). Our results showed that SNP rs8193036, which is located upstream of the coding region of the gene, was slightly associated with protection against T. cruzi infection (P=0.0170, P(FDR)=0.0851, odds ratio (OR)=0.80, confidence interval (CI)=0.66-0.96) and associated with protection against the development of cardiomyopathy (P=0.0065, P(FDR)=0.0324, OR=0.75, CI=0.60-0.92). This finding suggests that this IL17A polymorphism could be associated with Trypanosoma cruzi infection and the development of chronic cardiomyopathy due to differential expression of cytokine IL-17A.
Asunto(s)
Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Polimorfismo de Nucleótido Simple , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/patología , Colombia , Predisposición Genética a la Enfermedad , HumanosRESUMEN
This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.