Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Public Health. 2022 Aug 22;10:925303. doi: 10.3389/fpubh.2022.925303. eCollection 2022.
N6-Methyladenosine (m6A) is associated with many biological processes and the development of multiple diseases. The aim of this study was to analyze the association of m6A readers' genes variation, as well as their expression levels, with pulmonary tuberculosis (PTB). A total of 11 single-nucleotide polymorphisms (SNPs) in m6A readers' genes (i.e., rs6122103, rs6011668, rs602345, rs3738067, rs7464, rs12549833, rs3813832, rs17592288, rs2293596, and rs6594732, and rs2416282) were genotyped by SNPscan™ technique in 457 patients with PTB and 466 normal controls. The m6A readers' genes expression levels in peripheral blood mononuclear cells (PBMCs) from 78 patients with PTB and 86 normal controls were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). There was no significant association between all SNPs in , and genes and PTB susceptibility. The increased frequencies of rs3738067 GG genotype and rs3813832 CC genotype, C allele, were, respectively, found in PTB patients with hypoproteinemia and fever. rs6594732 variant was significantly associated with drug-induced liver damage and sputum smear-positive, and the rs2416282 variant was significantly associated with fever in patients with PTB. Compared with controls, the YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 mRNA levels were significantly decreased in PTB. Moreover, YTHDF1 level was negatively associated with erythrocyte sedimentation rate (ESR), and YTHDF3 and YTHDC1 levels were negatively related to alanine aminotransferase (ALT) in patients with PTB. Our results demonstrated that , and genes SNPs did not contribute to PTB susceptibility, while their decreased levels in patients with PTB suggested that these m6A readers might play significant roles in PTB.
N6-甲基腺苷（m6A）与许多生物过程和多种疾病的发展有关。本研究旨在分析 m6A 读取器基因变异及其表达水平与肺结核（PTB）的关系。对 11 个 m6A 读取器基因（rs6122103、rs6011668、rs602345、rs3738067、rs7464、rs12549833、rs3813832、rs17592288、rs2293596、rs6594732 和 rs2416282）的 11 个单核苷酸多态性（SNP）在 457 例 PTB 患者和 466 例正常对照者中进行 SNPscan™技术检测。用定量实时逆转录聚合酶链反应（qRT-PCR）检测 78 例 PTB 患者和 86 例正常对照者外周血单个核细胞（PBMCs）中 m6A 读取器基因的表达水平。所有基因和 PTB 易感性之间均无显著相关性。在低蛋白血症和发热的 PTB 患者中，发现 rs3738067 GG 基因型和 rs3813832 CC 基因型和 C 等位基因的频率增加。rs6594732 变异与药物性肝损伤和痰涂片阳性显著相关，rs2416282 变异与 PTB 患者发热显著相关。与对照组相比，PTB 患者的 YTHDF1、YTHDF2、YTHDF3、YTHDC1 和 YTHDC2 mRNA 水平明显降低。此外，YTHDF1 水平与红细胞沉降率（ESR）呈负相关，YTHDF3 和 YTHDC1 水平与丙氨酸氨基转移酶（ALT）呈负相关。我们的研究结果表明，基因 SNP 不影响 PTB 的易感性，而 PTB 患者的水平降低表明这些 m6A 读取器可能在 PTB 中发挥重要作用。
