Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Nosocomial Infection Management, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Immunol. 2022 Dec 7;13:992628. doi: 10.3389/fimmu.2022.992628. eCollection 2022.
The aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB).
A case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in (rs1061027, rs1139130, rs1061026), three SNPs in (rs62328061, rs4834698, rs1064034), and two SNPs in (rs1853259, rs11752345) were genotyped the SNPscan™ technique. , , and transcription levels were determined in 78 PTB patients and 86 controls quantitative real-time reverse-transcription PCR.
Frequencies of the rs62328061 GG genotype, rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. gene variation was not associated with PTB risk. The rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the rs62328061 G allele was associated with leukopenia, a reduced frequency of the rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, , , and transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase.
rs62328061 and rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.
本研究旨在探讨 m6A 甲基转移酶 METTL3、METTL14 和 WTAP 中的基因变异和转录水平在肺结核（PTB）中的作用。
设计了一项包括 461 例 PTB 患者和 467 例正常对照的病例对照研究，用于基因分型。采用 SNPscan™技术对三个 SNPs（rs1061027、rs1139130、rs1061026）、三个 SNPs（rs62328061、rs4834698、rs1064034）和两个 SNPs（rs1853259、rs11752345）进行基因分型。采用定量实时逆转录 PCR 检测 78 例 PTB 患者和 86 例对照的 、 、 和 转录水平。
与对照组相比，PTB 患者 rs62328061 GG 基因型、rs11752345 CT 基因型和 T 等位基因的频率显著增加。在 PTB 组中，rs62328061 的隐性模型检测到风险增加，rs11752345 的显性模型检测到风险降低。基因变异与 PTB 风险无关。rs1139130 GG 基因型与耐药性显著相关，rs1139130 G 等位基因与 PTB 患者的药物性肝损伤显著相关。rs62328061 G 等位基因频率降低与白细胞减少症相关，rs11752345 T 等位基因频率降低与痰涂片阳性相关，rs4834698 TC 基因型在低蛋白血症的 PTB 患者中更常见。与对照组相比，PTB 患者 、 、 和 转录水平显著降低，耐药性 PTB 患者 WTAP 水平升高。METTL3 水平与红细胞沉降率和天冬氨酸转氨酶呈负相关，METTL14 水平与丙氨酸转氨酶和天冬氨酸转氨酶呈负相关。
rs62328061 和 rs11752345 变异与 PTB 的遗传背景有关，METTL3、METTL14 和 WTAP 水平异常降低，提示这些 m6A 甲基转移酶可能在 PTB 中发挥重要作用。
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