Recent studies have revealed associations between genetic variants of LMP2 and LMP7 and infections with human papilloma virus7 and hepatitis B virus,8 and autoimmune conditions, such as ankylosing spondylitis.9

The study by Lv et al. makes a number of interesting findings regarding LMP2 and LMP7 and ITB.2 First, the risk ITB was significantly GW572016 higher in patients who were homozygous (odds ratio [OR] 3.86) or heterozygous (OR 2.28) for the genotype LMP7-145 GlnLys, but there was no increased risk for the LMP2-60 ArgCys variant. Second, the authors constructed four haplotypes combining the LMP2 and LMP7 genotypes. They then found an association between LMP2 Arg-LMP7 Lys and LMP2 Cys-LMP7 Lys and ITB, but with lower ORs of 1.87 and 1.83, respectively.

This confirms the association of the LMP7-Lys genotype with ITB, and raises the possibility that variation in LMP2 dampens the increased susceptibility conferred by the LMP7 polymorphism. selleckchem Third, the study found no association between LMP2/LMP7 polymorphisms and pulmonary TB. This may reflect differences in the immunological response to extra-pulmonary and pulmonary disease, or an insufficiently powered study. Further studies in larger populations are required to elucidate the mechanisms for this difference. These findings contribute to a growing body of knowledge about the complex interplay between genes and environment that result in an individual developing active TB.10,11 After direct exposure to M. tuberculosis, about 10% of people medchemexpress will progress to develop TB during their lifetime,12 and only a minority of these will develop ITB. Both host susceptibility and pathogen virulence factors play important roles in determining which infected individuals will develop TB. In addition to

the well-characterized causes of impaired host immunity, such as HIV, diabetes and immunosuppressive drugs, a growing number of genetic factors have been demonstrated over the past decade to confer an increased risk of active TB. A number of rare variants transmitted by Mendelian inheritance, affecting the genes for the interferon-gamma receptor (IFNγ-R1, IFNγ-R2), interleukin-12 receptor, STAT-1 and nuclear factor-kappa B (NF-κB), confer profound susceptibility to mycobacterial infections.11 In addition, case-control studies have identified common genetic polymorphisms in multiple genes that are associated with increased susceptibility to or protection against tuberculosis.10 Most of these studies have focused on pulmonary TB, but some have identified genetic variants with associations with extra-pulmonary disease, including loss-of-function polymorphisms in the purinergic P2X7 receptor on macrophages,13 and polymorphisms in the toll-Like receptor (TLR2) linked with TB meningitis.14 Whether these are genetic factors relating to extrapulmonary disease only or to all forms of TB requires further investigation.