講演情報
[O16-5]血中レジスチン濃度の人種横断型エピゲノムワイドメタ解析による新規DNAメチル化サイトの同定
○中杤 昌弘1, 市原 佐保子2, 山本 健3, 大中 佳三4, 松原 達昭5, 横田 充弘6 (1.名古屋大学大学院 医学系研究科 実社会情報健康医療学講座, 2.自治医科大学 医学部 環境予防医学講座, 3.久留米大学 医学部 医化学講座, 4.九州大学大学院医学研究院 先端医療医学部門, 5.愛知みずほ大学 人間科学部, 6.久留米大学 医学部)
Aims Human resistin is a biomarker or mediator of metabolic and inflammatory diseases. To investigate the epigenetic regulation of circulating resistin concentration, we performed a transethnic epigenome-wide meta-analysis.Methods Five studies comprised 622 Japanese and 944 German subjects based on the data from Illumina DNA methylation (DNAm) arrays. The association of DNAm level for each DNAm site with plasma resistin level was assessed using a general linear model with adjustment for age, sex, smoking status, and single nucleotide polymorphisms associated with resistin level. The results of the association analysis for each DNAm across the studies were combined using the fixed effects inverse variance-weighted method. Genome-wide significance was set at false discovery rate ＜ 10%. A replication study for the four identified DNAm sites was performed using profiles of 1033 Swedish subjects. Results Transethnic meta-analysis identified five DNAm sites that showed a significantly negative genome-wide association with resistin levels. Among the five sites, cg22322184, which is located in RETN, showed the most significant association, as we previously reported. The four remaining DNAm sites were novel. The replication study confirmed that two of these four DNAm sites, cg17723958 located at CCDC92 and cg17038235 located at ERGIC1, were significantly associated with resistin levels. Conclusions Our results indicate that resistin levels are epigenetically regulated by genes other than their own coding genes.