BAT1, a putative anti-inflammatory gene, is associated with chronic Chagas cardiomyopathy.
BACKGROUND
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- alpha and interferon- gamma ) 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.


METHODS
We 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.


RESULTS
Of 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.
Ramasawmy
Rajendranath
R
Heart Institute (InCor), University of São Paulo, Brazil. ramasawm@usp.br
Cunha-Neto
Edecio
E
Faé
Kellen C
KC
Müller
Natalie G
NG
Cavalcanti
Vanessa L
VL
Drigo
Sandra A
SA
Ianni
Barbara
B
Mady
Charles
C
Kalil
Jorge
J
Goldberg
Anna Carla
AC
D001938:Brazil; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000235:genetics*; D002908:Chronic Disease; D053487:DEAD-box RNA Helicases; D004247:DNA / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics*
D004247:DNA; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases