Genetic basis of tuberculosis susceptibility in India

Tuberculosis is a complex disease resulting from the responses of immunological, genetic and environmental factors to the chronic infectious agent, Mycobacterium tuberculosis. Several genetic factors have been implicated in host disease susceptibility and the prevalence of a disease in a population may be equal to the product of the frequencies of the susceptible alleles present in the population living in an endemic area. The endogamous, sympatrically isolated gene pools, exposed to the highly infectious environmental load of India, is an ideal model to study tuberculosis susceptibility. Our recent studies in this endemic region have reiterated the association of HLA-DRB1*02 and its subtype DRB1*1501 with tuberculosis susceptibility and have identified an IL-10 associated disease susceptibility in HLAnon-DRB1*02, BCG scar negative individuals and a skewed usage of TCR Vb in BCG scar negative, HLA high risk allele carrying individuals. This indicates that there may be several pathways leading to disease. Tuberculosis susceptibility is not thus a one-gene one product manifestation but multifactorial and epistatic influences of various factors finally lead to the disease. We review the factors that has been explored under Indian context in tuberculosis susceptibility.