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