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Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes

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Abstract

Background

Vitamin D (Vit. D) is used extensively during tuberculosis treatment. Low levels of serum Vit. D increase the risk of active tuberculosis development. Altered expression of the proteins involved in Vit. D metabolism impairs cathelicidin production, thereby increasing the host susceptibility to tuberculosis.

Objective

We are trying to investigate whether single nucleotide polymorphisms (SNPs) in LRP2, CUBN, and VDR genes could affect tuberculosis development.

Methods

We included participants of the Korean Association Resource (KARE), part of the Korean Genome and Epidemiology Study (KoGES), and used their recorded data. A total of 8840 people (4182 men and 4658 women) were eligible subjects. The 5-kb regions from the ends of transcripts of GC, LRP2, CUBN, and VDR genes were amplified to select 13, 47, 70, and 15 SNPs, respectively. For association analysis and statistical analysis, PLINK version 1.07 and PASW Statistics version 18.0 were used.

Results

Significant correlation was observed in 11, 2, and 1 SNPs in LRP2, CUBN, and VDR genes. The effect of rs6747692 of LRP2 on transcription factor binding was confirmed using RegulomeDB. We confirmed that rs2239182 of VDR is located in the genomic eQTL region and can affect transcription factor binding and gene expression.

Conclusions

Genetic polymorphisms in genes encoding proteins involved in Vit. D metabolism influence immune system components. Therefore, such polymorphisms may influence the susceptibility to Mycobacterium tuberculosis invasion and alter the defense mechanisms against Mycobacterium tuberculosis infection. The correlation between genetic variation and tuberculosis development can provide new guidelines for the management of tuberculosis.

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Acknowledgements

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Funding

This research was supported by the Academic Research Fund of Hoseo University in 2017 (20170054).

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Author notes

  1. Sung-Soo Kim and Sang In Lee are equal contributors.

Authors and Affiliations

  1. Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, 31499, Chungnam, Korea

    Sung-Soo Kim, Sang In Lee, Hyun-Seok Jin & Sangjung Park

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  1. Sung-Soo Kim
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  2. Sang In Lee
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  3. Hyun-Seok Jin
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  4. Sangjung Park
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Corresponding author

Correspondence to Sangjung Park.

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SSK, SIL, HSJ, SP declare that they have no conflict of interest.

Ethical approval

This study was approved by the institutional review board of the Korean National Institute of Health (KNIH) and Hoseo University (1041231–170418-h-056–02). Informed consent was obtained from all individual participants included in the study.

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Kim, SS., Lee, S.I., Jin, HS. et al. Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes. Genes Genom 42, 1189–1196 (2020). https://doi.org/10.1007/s13258-020-00971-3

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