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Genetic Effects on Sepsis and Pneumonia

The genetic risk for pneumonia, sepsis, and other serious infections is generally unrecognized or underestimated. Careful questioning of patients can detect a familial pattern of severe infection. Despite the strong evidence for a heritable risk of severe infection, the actual genetic factor(s) is not clear. The most likely genetic candidates are polymorphisms in components of the innate immune response. The best evidence to date is for polymorphisms in the tumor necrosis factor α, lymphotoxin α, and interleukin-1 receptor antagonist genes. Evidence for polymorphisms in other genes is reviewed. Presently, the clinical implication of this research is that patients with a strong family history of death from infection are candidates for immunization, even if they do not have other risk factors. However, these studies of genetic risk of infection have great promise for the future in understanding the pathogenesis of severe infections and in individualizing treatment.