Genetic and epigenetic factors affecting carotid intima-media thickness in monozygotic twins

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2024-11-14 DOI:10.1016/j.gene.2024.149093

Saho Mori , Yuya Arakawa , Mika Hasegawa , Shiho Kato , Hinako Hashimoto , Saki Yoshioka , Hiromichi Ueda , Osaka Twin Research Group , Mikio Watanabe

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Abstract

Background and aims

The intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins.

Methods

We measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins.

Results

We identified a CpG site (cg02432467) on HS3ST6 as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with LINC01006 expression and IMT-Cmax. Furthermore, there were significant differences in AP2A2 expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism.

Conclusions

We identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.

Abstract Image

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影响单卵双胞胎颈动脉内膜中层厚度的遗传和表观遗传因素。

背景和目的：颈动脉内膜厚度（IMT）是亚临床动脉粥样硬化的指标，其变化与糖尿病和免疫反应等各种因素密切相关。由于遗传和表观遗传因素，IMT 的变化程度因人而异。本研究旨在确定影响单卵双生子（MZ）颈动脉内径的单核苷酸多态性（SNPs）和 DNA 甲基化模式：方法：我们使用超声波测量了大阪大学双胞胎登记处招募的 107 对 MZ 双胞胎颈总动脉壁的最大 IMT（IMT-Cmax）和平均 IMT。使用珠子阵列对 SNPs 进行基因分型并测量甲基化水平，通过 RNA 测序确定每个基因的表达。对两组分别进行了线性回归分析：一组是从每对双胞胎中随机抽取，另一组是同卵双胞胎：结果：我们发现在 IMT-Cmax 和平均 IMT 分析中，HS3ST6 上的一个 CpG 位点（cg02432467）是一个重要的表观遗传因素。另一个位点（cg07927379）的甲基化水平与 LINC01006 的表达和 IMT-Cmax 呈负相关。此外，rs10902263多态性各基因型个体的AP2A2表达和平均IMT存在显著差异：我们发现了与颈动脉内径相关的遗传和表观遗传因素，这些因素可能有助于进行个体化评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.