Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul;30(3):323-8.
doi: 10.1007/s12291-014-0431-7. Epub 2014 Apr 11.

VDR, RXR, Coronin-1 and Interferonγ Levels in PBMCs of Type-2 Diabetes Patients: Molecular Link between Diabetes and Tuberculosis

Kirtimaan Syal  1 , Anand Srinivasan  2 , Dibyajyoti Banerjee  3
Affiliations

VDR, RXR, Coronin-1 and Interferonγ Levels in PBMCs of Type-2 Diabetes Patients: Molecular Link between Diabetes and Tuberculosis

Kirtimaan Syal et al. Indian J Clin Biochem. 2015 Jul.

Abstract

Diabetes and tuberculosis are world's most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-γ (PPARγ) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis. In this study, we checked the expression of RXR, VDR, TACO and Interferon-γ (IFNγ) genes in type-2 DM patients for understanding the link between the two diseases. We observed down regulation of RXR gene and corresponding up regulation of TACO gene expression. We have not observed significant change in expression of VDR and IFNγ genes in type-2 DM patients. Repression of RXR gene could hamper VDR-RXR heterodimer formation and thus would up regulate TACO gene expression which may predispose the type-2 DM patients to tuberculosis. Also, decrease in RXR-PPARγ heterodimer could be involved in DM.

Keywords: Diabetes; Molecular link; PPARγ; Risk factor; Tuberculosis; Vitamin A receptor (RXR); Vitamin D receptor (VDR).

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic view: RXR heterodimerizes with PPARγ and VDR to affect fatty acid/glucose metabolism and TACO protein expression respectively. Decrease in RXR- PPARγ heterodimer is responsible for diabetic state and increase in TACO expression is crucial for tuberculosis. RXR-VDR negatively regulates TACO expression. For details refer text
Fig. 2
Fig. 2
Densitometry analysis for estimation of expression levels of VDR, TACO, IFN-γ and RXR genes in peripheral blood mononuclear cells of diabetic patients (n = 15) in comparison to healthy controls (n = 8)
Fig. 3
Fig. 3
RXR functional binding partners network (www.string-db.org/)
Fig. 4
Fig. 4
Proposed link: If RXR expression is less then VDR would have less RXR to heterodimerize, thus reducing the levels of VDR-RXR heterodimer. Less RXR-VDR means more TACO expression which is known to be involved in pathogenesis of tuberculosis (For details, please refer text)
See this image and copyright information in PMC

References

    1. WHO. Global Prevalence of Diabetes, Estimates for the year 2000 and projections for 2030. 2004. - PubMed
    1. Raviglione MC, Snider DE, Jr, Kochi A. Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA. 1995;273(3):220–226. doi: 10.1001/jama.1995.03520270054031. - DOI - PubMed
    1. WHO. Tuberculosis Fact sheet N°104. 2013.
    1. Oni T, Stoever K, Wilkinson RJ. Tuberculosis, HIV, and type 2 diabetes mellitus: a neglected priority. Lancet Respir Med. 2013;1(5):356–358. doi: 10.1016/S2213-2600(13)70116-4. - DOI - PubMed
    1. Root HF. The association of diabetes and tuberculosis. N Engl J Med. 1934;210(3):127–147. doi: 10.1056/NEJM193401182100304. - DOI