Complement C3 F and BF S allotypes are risk factors for Chagas disease cardiomyopathy.

Abstract

The heterogeneity in the clinical expression of Chagas disease gives strong evidences for the involvement of genetic factors on its pathogenesis. Several studies have indicated different markers of genetic susceptibility to Chagas cardiomyopathy. In the present study, we present evidence of association between complement C3 and BF allotypes, and the susceptibility to Chagas disease and the development of cardiomyopathy. C3, BF, C4A, C4B and C2 polymorphism were determined in 100 seropositive Chagasic patients [cardiomyopathic (CARD), n = 57; asymptomatic indetermined (IND), n = 43] and in 100 non-related seronegative healthy controls. Patients and controls were matched according to their ethnic and geographical origin. A significantly increased frequency of C3F was observed in patients with the CARD form (8/57 14.03%), when compared with those presenting the IND form (0/43, 0%; RR 7.0) and with the healthy controls (5/100, 5%; RR 3.1). A negative association of the BF S allotype was observed in the CARD patients (19/57 33.33%) and in the Chagas total (38/100 38.0%), when compared with the controls (55/100, 55.0%; RR 0.4). All other C3, BF, C4A, C4B and C2 alleles showed no significant differences. These results suggest the allele C3F as a susceptible marker for the progression of the CARD form. On the other hand, BF S may represent a protective role against severe CARD disease. These results corroborate the importance of the alternative pathway in Trypanosoma cruzi infection and indicate possible genetic markers of Chagas cardiomyopathy.