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Association of genetic variations in the vitamin D pathway with susceptibility to tuberculosis in Kazakhstan

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Abstract

Tuberculosis (TB) poses an important health challenge and a significant economic burden for Kazakhstan and in Central Asia. Recent findings show a number of immunological related processes and host Mycobacterium tuberculosis defense are impacted by a variety of genes of the human host including those that play a part in the vitamin D metabolism. We investigated the genetic variation of genes in the vitamin D metabolic pathway of a cohort 50 TB cases in Kazakhstan and compared them to 34 controls living in the same household with someone infected with TB. We specifically analyzed 11 SNPs belonging to the following genes: DHCR7, CYP2R1, GC-1, CYP24A1, CYP27A1, CYP27B1, VDR and TNFα. These genes play a number of different roles including synthesis, activation, delivery and binding of the activated vitamin D. Our preliminary results indicate significant association of VDR (vitamin D receptor) SNPs (rs1544410, BsmI, with OR = 0.425, CI 0.221–0.816, p = 0.009 and rs731236, TaqI with OR = 0.443, CI 0.228–0.859, p = 0.015) and CYP24A1 (rs6013897 with OR = 0.436, CI 0.191–0.996, p = 0.045) with TB. Interaction of genetic variation of VDR and CYP24A1 may impact susceptibility to TB. The findings provided initial clues to understand individual genetic differences in relation to susceptibility and protection to TB.

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Acknowledgements

We like to acknowledge that the SNP genotyping was done with the support and the use of the SNP array developed by Fitgenes Pty Ltd, Melbourne Australia. We are grateful to Columbia University Global Health Research Center of Central Asia, Almaty and National TB Center, Almaty for organizational support of study participant recruitment.

Funding

This work was supported by the Nazarbayev University School of Medicine Social Policy Grant 2016 and by the Ministry of Education and Science of the Republic of Kazakhstan (Grants No. AP05134737, 0111RK00442).

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Authors and Affiliations

  1. Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 010000, Nur-Sultan, Kazakhstan

    Mukhtar Sadykov, Azliyati Azizan & Chee Kai Chan

  2. Laboratory of Genomic and Personalized Medicine, National Laboratory Astana, Nazarbayev University, 010000, Nur-Sultan, Kazakhstan

    Ulan Kozhamkulov, Ainur Akilzhanova & Dauren Yerezhepov

  3. University of South Florida College of Public Health, Tampa, FL, 33612, USA

    Max Salfinger

  4. University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA

    Max Salfinger

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  1. Mukhtar Sadykov
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Contributions

CKC, AAk, MS, AAz, UK conceptualized, design and coordinated the investigation. MS analyzed the data and carried out the statistical analysis. DY, AAk, UK participated in sample collection and DNA extraction. All authors participated in writing, reading and approval of the final manuscript.

Corresponding authors

Correspondence to Ulan Kozhamkulov or Chee Kai Chan.

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Conflict of interest

The authors declare that there no conflict of interest. Author CKC has minimal shares in Fitgenes Pte Ltd. Fitgenes Pte Ltd had no role in the design of the study; in the collection or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethics Committee of Center for Life Sciences, National Laboratory Astana, Kazakhstan. Informed consent was obtained from all individual participants included in the study.

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Sadykov, M., Azizan, A., Kozhamkulov, U. et al. Association of genetic variations in the vitamin D pathway with susceptibility to tuberculosis in Kazakhstan. Mol Biol Rep 47, 1659–1666 (2020). https://doi.org/10.1007/s11033-020-05255-3

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  • DOI: https://doi.org/10.1007/s11033-020-05255-3

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