BAT1, a Putative Anti-Inflammatory Gene, Is Associated with Chronic Chagas Cardiomyopathy

• Published in: The Journal of infectious diseases Vol. 193; no. 10; pp. 1394 - 1399
• Main Authors: Ramasawmy, Rajendranath, Cunha-Neto, Edecio, Faé, Kellen C., Müller, Natalie G., Cavalcanti, Vanessa L., Drigo, Sandra A., Ianni, Barbara, Mady, Charles, Kalil, Jorge, Goldberg, Anna Carla
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15-05-2006; University of Chicago Press; Oxford University Press
• Subjects: Alleles; Biological and medical sciences; Brazil; Cardiomyopathies; Chagas Cardiomyopathy - blood; Chagas Cardiomyopathy - genetics; Chagas disease; Chronic Disease; Chronic diseases; Cytokines; DEAD-box RNA Helicases; DNA - analysis; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genotypes; Heart; Heart diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Operating rooms; Parasites; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Promoter regions; Promoter Regions, Genetic - genetics; RNA Helicases - genetics; Trypanosoma cruzi; Brazil; Infection; Chronic; Gene; Microbiology; Cardiomyopathy; Heart disease; Cardiovascular disease; Myocardial disease
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/503368

BackgroundIt is not understood why only a subset of individuals infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC). Patients with CCC display high levels of circulating proinflammatory cytokines. Heart-infiltrating lymphocytes from patients with CCC also express proinflammatory cytokines (tumor necrosis factor–α and interferon-γ) that are detectable in biopsy samples and surgical heart-tissue samples. BAT1 a putative anti-inflammatory gene, presents functional polymorphisms in its promoter region that influence its transcriptional level MethodsWe assessed, by polymerase chain reaction restriction fragment–length polymorphism analysis, BAT1 variants in the promoter region at positions −22C/G and −348C/T in 154 patients with CCC and in 76 T. cruzi–infected but asymptomatic (ASY) patients ResultsOf the patients with CCC, 16% were homozygous for the −22C allele, compared with 4% of the ASY patients (P=.004; odds ratio [OR], 4.7 [95% confidence interval {CI}, 1.4–16]). A similar trend was observed for the −348C homozygotes (P=.01; OR, 1.9 [95% CI, 1.0–3.5]). Susceptibility to CCC was conferred by the C variants at nt −22 (P=.003; OR, 1.8 [95% CI, 1.2–2.8]) and at nt −348 (P=.02; OR, 1.7 [95% CI, 1.0–2.8]) ConclusionsBAT1 variants previously associated with reduced expression of HLA-B–associated transcript 1 are predictive of the development of CCC. These variants may be less efficient in down-regulating inflammatory responses and may contribute to the elevated production of proinflammatory cytokines in patients with CCC