Genetic susceptibility to mycobacterial disease in humans

Abstract

Summary Mycobacterial disease remains a serious global health problem. Tuberculosis causes more than 2 million deaths a year, and leprosy is still a cause of severe disability in many parts of the world. As a result of the study of individuals with marked susceptibility to usually nonpathogenic mycobacteria, as well as case-control studies with candidate genes and genome-wide screens of affected populations, there is substantial evidence for the role of genetic factors in the susceptibility to mycobacterial disease. These studies have defined immunological processes essential for the control of mycobacteria infections in humans.

Biomedical Importance of Host Genetic Factors in Infectious Diseases

“…A polymorphism with a 1513 A-C (rs3751143) that replaces the glutamic acid at residue 496 by alanine, was not associated with pulmonary TB in Gambia (Li et al, 2002). No link of 1513 SNP with pulmonary TB was found in Southeast Asian refugees from Australia but a strong association existed between the C polymorphism and extrapulmonary TB (Fernando et al, 2006).…”

“…Genetic polymorphisms and tuberculosis have been identified in several genes of host. A number of genes have been identified that play important role in tuberculosis (Fernando & Britton, 2006;Hoal, 2002). Several candidate gene studies and genome-wide linkage association studies (Bellamy et al, 2000;Jamieson et al, 2004;Miller et al, 2004;Cooke et al, 2008;Berrington & Hawn, 2007) have been performed for investigation of their role in disease risk.…”

Tuberculosis infection: Insight from immunogenomics

“…Human genetic studies indicate that variants in TLR pathway genes regulate the cellular immune response and may influence susceptibility to MTb [4,5,7,20]. A polymorphism in the signaling domain of TLR2 (G2258A (R753Q)) alters signaling in response to stimulation with lipopeptides as measured by NF-κB luciferase assays [21].…”

“…Early studies suggested associations of MHC variants and MTb susceptibility [7,20,36]. In addition, the discussion of variants in TLR pathway genes described above may impact DC function.…”

The P2X7 receptor and intracellular pathogens: a continuing struggle

“…When SNPs occur inside a gene, they create different variants, or alleles, of that gene. Genetic factors may confer protection or increase susceptibility to infectious disease [68,69]. P2X 7 receptor polymorphisms have been described in several diseases associated with loss-or gain-of-functions of this receptor.…”