Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.
Gene. 2021 Jun 20;786:145585. doi: 10.1016/j.gene.2021.145585. Epub 2021 Mar 20.
This study aimed to investigate the association of FTO methylation level with type 2 diabetes mellitus (T2DM) in a nested case-control study.
This nested case-control study included 287 pairs of T2DM cases and controls identified from a rural Chinese cohort study with a 6-year follow-up. Controls were matched to the cases on a 1:1 basis by age, sex, ethnicity, marital status, and residence. Conditional multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of cytosine guanine (CpG) locus and tag-single nucleotide polymorphisms (Tag-SNPs) with T2DM. Spearman correlation analysis was used to evaluate the association between FTO methylation and possible risk factors for T2DM in the control group.
The methylation level on the CpG9 site significantly differs between cases and controls, with a significant association between the CpG9 site methylation and probability of T2DM: OR 2.19 (95%CI: 1.31-3.65) after adjusting for potential confounders. The Tag-SNPs (rs72803657, rs1558902, rs17817449, rs11076023) were not associated with T2DM. Further, FTO methylation was associated with some risk factors for T2DM.
A CpG locus of FTO was positively associated with T2DM, but SNPs were not. FTO methylation were also associated with some T2DM risk factors. Further study with a large sample size and data on metabolic product are needed to confirm the association.
本研究旨在巢式病例对照研究中探讨 FTO 甲基化水平与 2 型糖尿病（T2DM）的相关性。
本巢式病例对照研究纳入了来自中国农村队列研究的 287 对 T2DM 病例和对照，随访时间为 6 年。对照与病例按年龄、性别、种族、婚姻状况和居住情况 1:1 匹配。采用条件多变量逻辑回归模型计算胞嘧啶鸟嘌呤（CpG）位点和标签单核苷酸多态性（Tag-SNP）与 T2DM 相关性的比值比（OR）和 95%置信区间（CI）。Spearman 相关分析用于评估 FTO 甲基化与对照组 T2DM 潜在危险因素之间的相关性。
病例组和对照组 CpG9 位点的甲基化水平存在显著差异，CpG9 位点的甲基化与 T2DM 发生的概率之间存在显著关联：调整潜在混杂因素后，OR 为 2.19（95%CI：1.31-3.65）。Tag-SNPs（rs72803657、rs1558902、rs17817449、rs11076023）与 T2DM 无关。此外，FTO 甲基化与 T2DM 的一些危险因素有关。
FTO 的 CpG 位点与 T2DM 呈正相关，但 SNP 无相关性。FTO 甲基化也与一些 T2DM 危险因素有关。需要进一步开展大样本量和代谢产物数据的研究来确认这种关联。
