State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Cell Physiol. 2020 Feb;235(2):900-908. doi: 10.1002/jcp.29005. Epub 2019 Jun 27.
Genetic variation is considered to affect the N -methyladenosine (m6A) RNA transcript modification, which is the most prevalent posttranscriptional messenger RNA modification. This study aimed to identify m6A-associated single-nucleotide polymorphisms (m6A-SNPs) that may affect m6A methylation from numerous periodontitis (PD) SNPs. We identified an abundance of m6A-SNPs by analyzing raw data of published PD genome-wide association studies and m6A-SNPs list from the m6AVar database. Other evidence was found in public databases for expression quantitative trait loci (eQTL) and differential gene expression analysis. Accordingly, 1938 m6A-SNPs were identified, 104 of which appeared to be associated with PD (p < .05) while 65 showed eQTL signals. Lastly, the leading SNP rs2723183 (p = 3.93E-07) was predicted to regulate local gene IL-37 expression in PD (p = 2.64E-05; in GSE10334) and change regulatory motif RXRA. In summary, dozens of PD-associated m6A-SNPs were identified and their possible functions were demonstrated in this study.
遗传变异被认为会影响 N-甲基腺苷(m6A)RNA 转录后修饰,这是最普遍的信使 RNA 转录后修饰。本研究旨在从众多牙周炎(PD)单核苷酸多态性(SNP)中鉴定可能影响 m6A 甲基化的 m6A 相关单核苷酸多态性(m6A-SNP)。我们通过分析已发表的 PD 全基因组关联研究的原始数据和 m6AVar 数据库中的 m6A-SNP 列表,鉴定出大量的 m6A-SNP。在公共数据库中还发现了表达数量性状基因座(eQTL)和差异基因表达分析的其他证据。据此,鉴定出 1938 个 m6A-SNP,其中 104 个似乎与 PD 相关(p <.05),而 65 个显示出 eQTL 信号。最后,主要 SNP rs2723183(p = 3.93E-07)被预测可调节 PD 中局部基因 IL-37 的表达(p = 2.64E-05;在 GSE10334 中)并改变调节基序 RXRA。总之,本研究鉴定了数十个与 PD 相关的 m6A-SNP,并证明了它们的可能功能。