INTRODUCTION Late-onset Alzheimer disease (LOAD) is the most common dementia worldwide. APOE-[Latin Small Letter Open E]4 and BIN1 (Bridging Integrator 1) have been implicated in the pathogenesis of this disease, but, although DNA methylation of dinucleotide CpGs in the BIN1 gene influences alterations, it has not been studied in Hispanics. OBJECTIVE The objective of this study was to evaluate the BIN1 3' intergenic region DNA methylation patterns in a Colombian sample of LOAD patients. METHODS A case-control study was conducted in 50 individuals with LOAD and 50 age-sex matched controls to determine associations of LOAD with DNA methylation. DNA was isolated from peripheral blood, and methylation levels of 8 CpGs were estimated by bisulfite conversion followed by Sanger sequencing with direct PCR analysis. Logistic regression models adjusted by age, sex, and APOE were used to calculate risk associations between methylation levels and LOAD. RESULTS Overall, participants with LOAD had significantly lower methylation levels on CpG26 (0.86±0.11 vs. 0.95±0.05; P>0.001), CpG44 (0.84±0.09 vs. 0.94±0.06; P=0.001), and CpG87 (0.64±0.12 vs. 0.82±0.10; P>0.001). Adjusted regression models showed that decreased methylation levels of these CpGs remained as risk factors for LOAD (P<0.05). CONCLUSIONS Hypomethylation of CpGs in BIN1 might play an important role in the expression of BIN1 and may be a biomarker for identifying individuals at high risk of developing LOAD.

中文翻译：

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阿尔茨海默氏病患者中BIN1基因CpG的甲基化水平差异。

引言迟发性阿尔茨海默病（LOAD）是全世界最常见的痴呆症。APOE- [拉丁文小写字母E] 4和BIN1（桥接整合子1）已与该病的发病机制有关，但是，尽管BIN1基因中二核苷酸CpG的DNA甲基化会影响其改变，但尚未在西班牙裔中进行研究。目的本研究的目的是评估哥伦比亚LOAD患者的BIN1 3'基因间区域DNA甲基化模式。方法对50名患有LOAD的个体和50名年龄性别匹配的对照者进行病例对照研究，以确定LOAD与DNA甲基化的关联。从外周血中分离DNA，通过亚硫酸氢盐转化，然后通过Sanger测序和直接PCR分析，估算8 CpG的甲基化水平。通过年龄，性别和APOE调整的Logistic回归模型用于计算甲基化水平和LOAD之间的风险关联。结果总体而言，LOAD参与者的CpG26甲基化水平显着降低（0.86±0.11 vs.0.95±0.05; P> 0.001），CpG44（0.84±0.09 vs.0.94±0.06; P = 0.001）和CpG87（0.64±0.12） vs.0.82±0.10； P> 0.001）。调整后的回归模型显示，这些CpG甲基化水平降低仍然是LOAD的危险因素（P <0.05）。结论BIN1中CpGs的甲基化可能在BIN1的表达中起重要作用，并且可能是鉴定具有高发生LOAD风险的个体的生物标记。LOAD参与者的CpG26（0.86±0.11 vs.0.95±0.05; P> 0.001），CpG44（0.84±0.09 vs.0.94±0.06; P = 0.001）和CpG87（0.64±0.12 vs.0.82）的甲基化水平明显降低±0.10; P> 0.001）。调整后的回归模型显示，这些CpG甲基化水平降低仍然是LOAD的危险因素（P <0.05）。结论BIN1中CpGs的甲基化可能在BIN1的表达中起重要作用，并且可能是鉴定具有高发生LOAD风险的个体的生物标记。LOAD参与者的CpG26（0.86±0.11 vs.0.95±0.05; P> 0.001），CpG44（0.84±0.09 vs.0.94±0.06; P = 0.001）和CpG87（0.64±0.12 vs.0.82）的甲基化水平明显降低±0.10; P> 0.001）。调整后的回归模型显示，这些CpG甲基化水平降低仍然是LOAD的危险因素（P <0.05）。结论BIN1中CpGs的甲基化可能在BIN1的表达中起重要作用，并且可能是鉴定具有高发生LOAD风险的个体的生物标记。