Tuberculosis risk is associated with genetic polymorphisms in the LRP2 , CUBN , and VDR genes
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Genes & Genomics https://doi.org/10.1007/s13258-020-00971-3
RESEARCH ARTICLE
Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes Sung‑Soo Kim1 · Sang In Lee1 · Hyun‑Seok Jin1 · Sangjung Park1 Received: 5 September 2019 / Accepted: 13 July 2020 © The Genetics Society of Korea 2020
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. Keywords Tuberculosis · LRP2 · CUBN · VDR · Polymorphisms
Introduction Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (MTB) infection, and 1/3rd of the world’s population is infected with TB (Dolin et al. 1994; Jasmer et al. 2002). TB can be divided into latent TB and active TB Sung-Soo Kim and Sang In Lee are equal contributors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13258-020-00971-3) contains supplementary material, which is available to authorized users. * Sangjung Park [email protected] 1
Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan 31499, Chungnam, Korea
based on disease progression. Most of mycobacterial infections are associated with latent TB, which is not clinically symptomatic. In latent TB, MTB can survive in host macrophages. However, when the immune system of the host is weakened, the MTB becomes active, leading to ac
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