title: Lack of association of tumor necrosis factor-alpha polymorphisms with Chagas disease in Brazilian patients.
abstract: One third of Trypanosoma cruzi-infected individuals develop chronic Chagas disease cardiomyopathy (CCC) while the majority remains asymptomatic (ASY). About 30% of CCC patients develop heart failure due to end-stage inflammatory dilated cardiomyopathy. Increased production of tumor necrosis factor (TNF)-alpha has been described in all clinical forms of Chagas disease, and the highest levels are detected in CCC patients with severe ventricular dysfunction. Genetic susceptibility may play a role in the clinical outcome of Chagas disease. We investigated TNF as a candidate gene for susceptibility to development and/or progression of CCC. We analyzed the TNFa microsatellite and the -308 TNF promoter polymorphisms, in 166 CCC compared to 80 ASY geographically and age-matched patients in an association study. To analyze the association of TNF polymorphisms with progression of the cardiomyopathy, CCC patients were also grouped in three categories according to degree of left ventricular (LV) dysfunction into severe (n=57), mild to moderate (n=21) and absent (n=88). Our results show no significant differences either between CCC and ASY patients, or among CCC patients according to severity of cardiomyopathy with respect to TNFa or -308 TNF promoter polymorphisms. These results indicate that TNF polymorphisms are associated neither to CCC development nor to progression to more severe forms of cardiomyopathy in Brazilian Chagas disease patients.
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Drigo
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: Bárbara
authors.initials: B
authors.lastname: Ianni
authors.forename: Charles
authors.initials: C
authors.lastname: Mady
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Faé
authors.forename: Paula
authors.initials: P
authors.lastname: Buck
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Anna Carla
authors.initials: AC
authors.lastname: Goldberg
mesh_terms: D001938:Brazil / Q000453:epidemiology; D002598:Chagas Cardiomyopathy / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha