HLA-B35 and MICA-A5 synergistically enhanced the susceptibility to Chagas heart disease

Abstract

[Summary] To determine the host genetic factors that influence susceptibility to Chagas heart disease, we typed 33 unrelated, seropositive Chagas patients with cardiac disorders at the Department of Cardiology, Zacapa National Hospital, Zacapa, Guatemala, and 138 seronegative controls for polymorphisms of HLA-B, MHC class I chain-related gene A (MICA), and the Tumor Necrosis Factor-a (TNF-a) promoter region. The frequency of BLA-B35 was significantly increased in the cardiac Chagas patients (Pc<0.003, OR = 5.50, 95%CI=2.31-13.11). Although there was no association between MICA, TNF-a promoter region polymorphisms and the disease, the increased risk for the individuals who had both HLA-B35 and MICA-A5 (delta odds ratio; ORB_35 /A5 -1=9.80) was higher than the sum of the increased risks for either HLA-B35 (DR_B35 -1=2.78) or MICA-A5 single positive (OR_A5 -1=0.08) individuals, indicating that the effects of the two alleles on susceptibility were synergistic.