The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB.
However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population.
A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.
These results support the influence of TIRAP (MAL) S180L polymorphism on TB and indicate that TB and SLE might share a common immunogenetic pathway in the innate immune response.
However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population.
We conclude that TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis and may be a new risk factor for the development of tuberculosis in China.