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.

中文翻译：

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结核病风险与 LRP2、CUBN 和 VDR 基因的遗传多态性相关。

背景

维生素 D (Vit. D) 在结核病治疗期间被广泛使用。血清维生素含量低。D 增加活动性结核病发展的风险。Vit 中涉及的蛋白质的表达改变。D 代谢会损害导管素的产生，从而增加宿主对结核病的易感性。

客观的

我们正在尝试研究LRP2、CUBN和VDR基因中的单核苷酸多态性 (SNP) 是否会影响结核病的发展。

方法

我们纳入了韩国协会资源 (KARE)、韩国基因组和流行病学研究 (KoGES) 的一部分的参与者，并使用了他们的记录数据。共有 8840 人（4182 名男性和 4658 名女性）为合格受试者。GC、LRP2、CUBN和VDR基因转录本末端的 5-kb 区域分别被扩增以选择13、47、70和 15 个 SNP。对于关联分析和统计分析，使用了 PLINK 1.07 版和 PASW Statistics 18.0 版。

结果

在LRP2、CUBN和VDR基因中的11、2和 1 个 SNP 中观察到显着相关性。使用 RegulomeDB 证实了 LRP2 的rs6747692对转录因子结合的影响。我们证实VDR 的rs2239182位于基因组 eQTL 区域，可以影响转录因子结合和基因表达。

结论

编码与 Vit 相关的蛋白质的基因的遗传多态性。D 代谢影响免疫系统成分。因此，这种多态性可能会影响对结核分枝杆菌入侵的易感性，并改变对结核分枝杆菌感染的防御机制。遗传变异与结核病发展之间的相关性可以为结核病的管理提供新的指导方针。