Chagas= disease (American trypanosomiasis) is a leading cause of heart disease in Latin America, affecting between 16 and 18 million individuals. In Brazil alone, approximately 10% of the population is seropositive for T. Cruzi, the parasitic cause of the disease, with sub-populations experiencing seropositivity as high as 65%. Given the large pool of primary hosts for this zoonotic disease, complete eradication of Chagas= disease through control of the arthropod vector is unlikely. In fact, prevalence of the disease is rising in many urban areas of South America and is being introduced into new rural areas with changing migration patterns. Research with humans and animal models indicates that there is variation in both susceptibility to infection and the physiological risk factors for infection. This study will determine the genetic components of susceptibility to T. Cruzi infection by assessing infection status, quantitative lipoprotein and immunological risk factors for T. Cruzi infection and approximately 200 genetic markers distributed across the genome in 1500 adult residents of the municipality of Posse, in rural Goias, Brazil. Statistical genetic analyses of the resulting data will be used to characterize and locate the genetic factors influencing the susceptibility to infection with t. Cruzi. Additionally, the specific hypothesis that susceptibility to T. Cruzi infection is associated inversely with gene copy number of the active component of the trypanosome lytic fact (TLF) (i.e., haptoglobin- related protein) and directly with plasma concentration of a potent inhibitor of TLF, haptoglobin, will be susceptibility to infection with T. Cruzi, 2) to delineate the ways in which these genes interact with each other and with genes that influence immunological and lipoprotein risk factors for the T. Cruzi infection, and 3) to suggest new areas for targeting prevention and biologic intervention programs.
