Associations Between Tuberculosis Risk And Variants Of Diabetes

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Tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, which is thought to be predominately spread by coughing. According to the World Health Organization (WHO), around a quarter of the world’s population is infected with M. tuberculosis. Infection does not always develop into symptomatic TB. The majority of TB cases afflict the lungs, but other sites in the body can be affected as well. In 2017 there were 1.6 million deaths due to TB.

Diabetes is a risk factor for TB, however the underlying mechanism is not well understood. Yan V. Sun of Emory University, Atlanta, USA, led a study that investigated whether previously identified host genetic variants associated with infection susceptibility to TB and progression were associated with UK Biobank genetic loci of diabetes. The results were published in the journal Open Forum Infectious Diseases.

TB risk was associated with the HLA-DRA-DQA1 locus in people with type I diabetes. In type II diabetics, HLA and ASAP1 loci were associated with increased odds of disease. One of the genes in the HLA region is BTNL2, which belongs to the butyrophilin-like B7 family of proteins involved in immune surveillance. It is a negative regulator of T-cell proliferation and cytokine release.

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The ASAP1 gene encodes a multidomain ADP-ribosylation factor GTPase activating protein, which regulates dynamics of the cytoskeleton, receptor dynamics, and intracellular vesicle trafficking.

The study is limited by the fact that TB risk loci were obtained from non-europeans whereas the diabetes loci were identified in predominantly european ancestry volunteers in the UK biobank. The risk loci for TB may be different in people with European ancestry. This highlights the need for more diabetes cohorts in a wider range of populations.

“Our results support the hypothesis that TB-associated host genetic factors are also associated with via immunologic functions. Moreover, common genetic factors and pathways may exist more broadly between other infectious and metabolic diseases, particularly via molecular mechanisms associated with defense against infectious pathogens. A better understanding of the underlying relationships between infectious and chronic diseases may be particularly important for developing countries with a high prevalence of both,” concluded the authors.