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白细胞内长散在核元件-1 DNA 甲基化与日本一般人群血脂异常的关系。

Relationship between Long Interspersed Nuclear Element-1 DNA Methylation in Leukocytes and Dyslipidemia in the Japanese General Population.

机构信息

Clinical Laboratory Medicine, Fujita Health University Graduate School of Health Sciences.

Department of Hygiene, Fujita Health University School of Medicine.

出版信息

J Atheroscler Thromb. 2018 Dec 1;25(12):1231-1239. doi: 10.5551/jat.43570. Epub 2018 Apr 7.

Abstract

AIM

Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population.

METHODS

We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method.

RESULTS

Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval [CI], 1.20-2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20-3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11-4.82).

CONCLUSION

LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism.

摘要

目的

异常的全基因组 DNA 甲基化与多种疾病的发生有关,包括心血管疾病(CVD)。我们研究了白细胞中长散布核元件-1(LINE-1)的甲基化是否与血脂异常有关,血脂异常是 CVD 的一个主要危险因素。

方法

我们进行了一项横断面研究,共纳入 420 名日本受试者(187 名男性和 233 名女性),他们没有癌症、中风或缺血性心脏病的临床病史。使用焦磷酸测序法测量白细胞中 LINE-1 DNA 甲基化水平。

结果

与相应的正常组相比,高 LDL 胆固醇和高 LDL/HDL 比值组的 LINE-1 高甲基化比值的优势比(OR)显著更高(高 LDL-C 组:OR,1.88;95%置信区间 [CI],1.20-2.96;高 LDL/HDL 比值组:OR,1.90;95%CI,1.20-3.01)。与无脂质异常的受试者相比,有 2 种或更多脂质异常的受试者的 LINE-1 高甲基化比值的 OR 显著更高(OR,2.31;95%CI,1.11-4.82)。

结论

白细胞中 LINE-1 DNA 的高甲基化与 CVD 风险谱有关:高 LDL-C、高 LDL/HDL 比值和异常脂质代谢程度。

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