血脂异常症中 DNA 甲基化的遗传分析:病例对照研究。
Genetic analysis of DNA methylation in dyslipidemia: a case-control study.
机构信息
First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, China.
出版信息
PeerJ. 2022 Dec 19;10:e14590. doi: 10.7717/peerj.14590. eCollection 2022.
BACKGROUND
Coronary heart disease has become the leading cause of death in developed countries, and dyslipidemia is closely associated with the risk of cardiovascular disease. Dyslipidemia is caused by the abnormal regulation of several genes and signaling pathways, and dyslipidemia is influenced mainly by genetic variation. , and genes are associated with lipid metabolism. In a recent GWAS study, the gene has been reported to be associated with dyslipidemia, but its molecular mechanism has not been thoroughly investigated. The correlation between the DNA methylation of these genes and lipid metabolism has not been studied. This study aimed to examine the relationship between the DNA methylation of these genes and the risk of dyslipidemia by comparing the methylation levels of dyslipidemia and control samples.
METHODS
A case-control research method was used in this study. The patient's blood samples were collected at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. In the Xinjiang Han population, 100 cases of hyperlipidemia and 80 cases of the control group were selected. The two groups were age and gender-matched. Quantitative methylation analysis of CpG sites in the gene promoter regions of six genes was performed by Solexa high-throughput sequencing.
RESULTS
The DNA methylation levels of 23 CpG sites in six genes were shown to be associated with hyperlipidemia, and a total of 20 DNA methylation haplotypes showed statistically significant differences between the two groups. When compared with the control group, the dyslipidemia group had significantly higher levels of methylation in the gene (2.68 2.36, = 0.04). Additionally, we also discovered a significant methylation haplotype of GRINA ( = 0.017).
CONCLUSION
The findings of this study reveal that the DNA methylation of increases the risk for dyslipidemia in humans.
背景
冠心病已成为发达国家的主要致死原因,而血脂异常与心血管疾病的风险密切相关。血脂异常是由几个基因和信号通路的异常调节引起的,血脂异常主要受遗传变异的影响。LPL、CETP 和 APOA5 等基因与脂质代谢有关。在最近的 GWAS 研究中,已经报道了基因与血脂异常有关,但它的分子机制尚未得到彻底研究。这些基因的 DNA 甲基化与脂质代谢之间的相关性尚未得到研究。本研究旨在通过比较血脂异常和对照组的甲基化水平,来研究这些基因的 DNA 甲基化与血脂异常风险之间的关系。
方法
本研究采用病例对照研究方法。采集新疆医科大学第一附属医院心脏中心患者的血液样本。在新疆汉族人群中,选择 100 例高脂血症患者和 80 例对照组。两组年龄和性别匹配。采用 Solexa 高通量测序技术对 6 个基因启动子区 CpG 位点的 DNA 甲基化进行定量分析。
结果
6 个基因的 23 个 CpG 位点的 DNA 甲基化水平与高脂血症有关,两组之间共有 20 个 DNA 甲基化单倍型存在统计学差异。与对照组相比,血脂异常组基因(2.68 ± 2.36,= 0.04)的甲基化水平显著升高。此外,我们还发现了一个显著的 GRINA 甲基化单倍型(= 0.017)。
结论
本研究结果表明,基因的 DNA 甲基化增加了人类发生血脂异常的风险。
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