Which genes increase or decrease the risk of typhoid fever (enteric fever)?

Updated: Aug 19, 2019
  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

Other risk factors for typhoid fever include various genetic polymorphisms. These risk factors often also predispose to other intracellular pathogens. For instance, PARK2 and PACGR code for a protein aggregate that is essential for breaking down the bacterial signaling molecules that dampen the macrophage response. Polymorphisms in their shared regulatory region are found disproportionately in persons infected with Mycobacterium leprae and S typhi. [11]

On the other hand, protective host mutations also exist. The fimbriae of S typhi bind in vitro to cystic fibrosis transmembrane conductance receptor (CFTR), which is expressed on the gut membrane. Two to 5% of white persons are heterozygous for the CFTR mutation F508del, which is associated with a decreased susceptibility to typhoid fever, as well as to cholera and tuberculosis. The homozygous F508del mutation in CFTR is associated with cystic fibrosis. Thus, typhoid fever may contribute to evolutionary pressure that maintains a steady occurrence of cystic fibrosis, just as malaria maintains sickle cell disease in Africa. [19, 20]


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