BAT1, a Putative Anti-Inflammatory Gene, Is Associated with Chronic Chagas Cardiomyopathy
R Ramasawmy, E Cunha-Neto, KC Faé… - The Journal of …, 2006 - academic.oup.com
R Ramasawmy, E Cunha-Neto, KC Faé, NG Müller, VL Cavalcanti, SA Drigo, B Ianni…
The Journal of infectious diseases, 2006•academic.oup.comBackground It 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 …
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 …
Abstract
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])
Conclusions BAT1 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
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