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中国西部结核病患者 lnc-AC145676.2.1-6 和 lnc-TGS1-1 及其变体的临床意义。

Clinical significance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in western Chinese tuberculosis patients.

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China.

出版信息

Int J Infect Dis. 2019 Jul;84:8-14. doi: 10.1016/j.ijid.2019.04.018. Epub 2019 Apr 24.

Abstract

OBJECTIVES

Tuberculosis (TB) remains a global public health problem. Recent studies have implicated long non-coding RNAs and their variants as possibly playing important roles in TB. The aim of this study was to assess the clinical relevance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in a western Chinese population.

METHODS

This case-control study included 467 TB patients and 473 healthy controls from West China Hospital. The expression levels of lnc-AC145676.2.1-6 and lnc-TGS1-1 were analyzed by reverse transcriptase quantitative real-time PCR. Single-nucleotide polymorphism genotyping was performed using a custom-designed 2 × 48-Plex SNPscan kit.

RESULTS

It was observed that lnc-AC145676.2.1-6 and lnc-TGS1-1 expression levels were both obviously down-regulated in TB patients. In addition, a lower expression level of lnc-TGS1-1 was associated with the presence of thrombocytopenia in TB patients during anti-TB treatment, and the homozygous CC genotype of rs4737420 correlated with a decreased risk of leukopenia, compared with individuals with the T allele (TT/CT genotype), in the dominant mode.

CONCLUSIONS

For the first time, potential TB-associated promoting effects were identified for the decreased expression levels of lnc-AC145676.2.1-6 and lnc-TGS-1, while lnc-TGS1-1 and its variant rs4737420 may be predictive indicators of anti-TB drug-induced adverse drug reactions. Larger validation studies on different populations are warranted to confirm these findings.

摘要

目的

结核病(TB)仍然是一个全球性的公共卫生问题。最近的研究表明,长非编码 RNA 及其变体可能在结核病中发挥重要作用。本研究旨在评估长非编码 RNA AC145676.2.1-6 和 TGS1-1 及其变体在西方中国人群中的临床相关性。

方法

这项病例对照研究纳入了来自华西医院的 467 例 TB 患者和 473 名健康对照者。采用逆转录定量实时 PCR 分析长非编码 RNA AC145676.2.1-6 和 TGS1-1 的表达水平。采用定制的 2×48-Plex SNPscan 试剂盒进行单核苷酸多态性基因分型。

结果

研究发现,TB 患者的长非编码 RNA AC145676.2.1-6 和 TGS1-1 表达水平均明显下调。此外,在抗结核治疗过程中,TB 患者血小板减少与长非编码 RNA TGS1-1 表达水平降低有关,与 T 等位基因(TT/CT 基因型)相比,rs4737420 纯合 CC 基因型与白细胞减少的风险降低相关,呈显性模式。

结论

这是首次发现长非编码 RNA AC145676.2.1-6 和 TGS-1 的表达水平降低与结核病相关的潜在促进作用,而长非编码 RNA TGS1-1 及其变体 rs4737420 可能是抗结核药物不良反应的预测指标。需要在不同人群中进行更大规模的验证研究来证实这些发现。

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