Host genetics and tuberculosis: Theory of genetic polymorphism and tuberculosis

Tuberculosis (TB), the leading cause of morbidity and mortality by a single infectious agent, Mycobacterium tuberculosis, is still a major health problem in the world. To date, many studies have shown evidence of association between host genetic polymorphisms and TB susceptibility, including chemokine (C-C motif) ligand 2 (CCL-2)/monocyte chemoattractant protein1 (MCP-1), natural resistance-associated macrophage protein 1 (NRAMP-1)/solute carrier protein 11A1 (SLC11A1), Immunity-related GTPase family M protein (IRGMI), interleukin (IL)-8, toll-like receptor (TLR), and nucleotide-binding oligomerization domain containing protein-2 (NOD-2) genes. Most of these genes participate in immune response, and their polymorphism can alter immunity and lead to genetic susceptibility to TB.

This is a special article compiled with reference to various case-control studies, meta-analysis, and other research work on different genes and TB. The genes selected and a number of studies from different countries and ethnic groups for this article are shown below. The genes selected for the study are: NRAMP-1 (SLC11 A1), Vitamin D receptor, low molecular weight polypeptide/transporter with antigen processing, CCL-2/MCP-1, IRGM-1, IL-1, IL-8, IL-10, IL-12, TLR, NOD-2, human leukocyte antigen, mannose-binding lectin, major histocompatibility complex, tumor necrosis factor, P2X 7, epiregulin, SP110, and interferon gamma (IFN-gamma).

Genetic polymorphisms in different genes showed variable levels of significance in relation to TB. All these were proved by the researchers using appropriate statistical methods and tools.

Based on different research works across the world, there is sufficient evidence to prove that TB is a genetically primed and determined infectious disease caused by M. tuberculosis and the genetic polymorphism is the mechanism that leads to progression from infection to TB disease. Why only 10-15% of the people infected with M. tuberculosis progress toward TB disease has continued to be an unresolved debate. Hence, for provoking thoughts and encouraging more research in the field of genetics and TB I formulated hypothesis and algorithms, and theory. Genetic susceptibility to TB has been substantiated based on the extensive literature review and the research findings that are well narrated.