Department of Biophysics, Pamukkale University School of Medicine, Denizli, Turkey.
Department of Molecular, Cell and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, CA, U.S.A.
In Vivo. 2020 Jan-Feb;34(1):361-367. doi: 10.21873/invivo.11782.
BACKGROUND/AIM: This study aimed to measure the DNA methylation state of thousands of CpG islands in the blood of two monozygotic twins that were discordant for cardiovascular disease (CVD). Twin 1 had suffered myocardial infarction, while the other was healthy.
Since the aim of this study was to identify differentially methylated regions which might act as potential markers, reduced-representation bisulfite libraries were used for whole-genome methylation analysis.
According to the analysis, 11 genes lipid droplet associated hydrolase (LDAH), apolipoprotein B (APOB), acyl-CoA synthetase medium chain family member 2A (ACSM2A), acyl-CoA synthetase medium chain family member 5(ACSM5), acyl-CoA synthetase family member 3 (ACSF3), carboxylesterase 1 (CES1), carboxylesterase 1 pseudogene 1 (CES1P1), AFG3 like matrix AAA peptidase subunit 2 (AFG3L2), iron-sulfur cluster assembly enzyme (ISCU), SEC14 like lipid binding 2 (SEC14L2) and microsomal triglyceride transfer protein (MTTP) were all hypomethylated in DNA from twin 2, the unaffected twin. Methylation changes were observed at different multiple loci between the twins, suggesting loci that are affected by disease status in identical genetic backgrounds.
This twin study may contribute significantly to the understanding of the genetic basis of CVD and resulting myocardial infarction. This approach may allow identification of possible target loci associated with aberrant epigenetic regulation in CVD.
背景/目的：本研究旨在测量一对在心血管疾病（CVD）方面存在差异的同卵双胞胎的血液中数千个 CpG 岛的 DNA 甲基化状态。双胞胎 1 患有心肌梗死，而另一个则健康。
由于本研究的目的是确定可能作为潜在标志物的差异甲基化区域，因此使用了简化代表性双硫酸盐文库进行全基因组甲基化分析。
根据分析，11 个基因（脂质滴相关水解酶（LDAH）、载脂蛋白 B（APOB）、酰基辅酶 A 合成酶中链家族成员 2A（ACSM2A）、酰基辅酶 A 合成酶中链家族成员 5（ACSM5）、酰基辅酶 A 合成酶家族成员 3（ACSF3）、羧酸酯酶 1（CES1）、羧酸酯酶 1 假基因 1（CES1P1）、AFG3 样基质 AAA 肽酶亚基 2（AFG3L2）、铁硫簇组装酶（ISCU）、SEC14 样脂结合蛋白 2（SEC14L2）和微粒体甘油三酯转移蛋白（MTTP）在未受影响的双胞胎 2 的 DNA 中均呈低甲基化。双胞胎之间在多个不同的基因座观察到甲基化变化，这表明基因座受相同遗传背景下疾病状态的影响。
这项双胞胎研究可能对理解 CVD 和由此导致的心肌梗死的遗传基础有重大贡献。这种方法可能允许鉴定与 CVD 中异常表观遗传调控相关的可能靶基因座。
