Evidence that genetic susceptibility to Mycobacterium tuberculosis in a brazilian population is under oligogenic control: Linkage study of the candidate genes NRAMP1 and TBFA

Abstract Setting: A study of multicase tuberculosis pedigrees from Northern Brazil. Objective: To determine the model of inheritance for genetic susceptibility to tuberculosis, and to test the hypothesis that TNFA and NRAMP1 are candidate susceptibility genes. Design: The study sample included 98 pedigrees, 704 individuals and 205 nuclear families. Segregation analyses were performed using the programs POINTER and COMDS. Combined segregation and linkage analysis was carried out within COMDS. Non-parametric linkage analyses were performed using BETA. Results: A sporadic model for disease distribution in families was strongly rejected, as were polygenic and multifactorial models. A codominant single gene model provided the best fit ( P P P = 0.039; D2S1471, P = 0.025) tightly linked ( Conclusions: Tuberculosis susceptibility in this region of Brazil is under oligogenic control. Although a minor role for TNFA and NRAMP1 cannot be excluded, our data suggest that neither is a major gene involved in this oligogenic control.