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血管紧张素 I 转化酶基因多态性和全基因组 DNA 甲基化在尿中二-(2-乙基己基)邻苯二甲酸代谢物与血清脂联素在年轻台湾人群中呈负相关关系中的作用。

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population.

机构信息

Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, 237, Taiwan.

School of Medicine, Fu Jen Catholic University, New Taipei City, 242, Taiwan.

出版信息

Clin Epigenetics. 2023 May 17;15(1):87. doi: 10.1186/s13148-023-01502-z.

Abstract

BACKGROUND

Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood.

METHODS

This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12-30 from Taiwan.

RESULTS

Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (- 0.095 vs. - 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG.

CONCLUSIONS

In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

摘要

背景

脂联素是脂肪组织中产生的一种关键蛋白,在多种代谢过程中起着至关重要的作用。邻苯二甲酸二(2-乙基己基)酯(DEHP)作为一种增塑剂,已被证明在体外和体内研究中降低脂联素水平。然而,血管紧张素转换酶(ACE)基因多态性和表观遗传变化在 DEHP 暴露与脂联素水平之间的关系中的作用尚不清楚。

方法

本研究在来自台湾的 699 名 12-30 岁个体的样本中,检查了尿液 DEHP 代谢物水平、表观遗传标志物 5mdC/dG、ACE 基因表型与脂联素水平之间的相关性。

结果

结果显示,单-2-乙基己基邻苯二甲酸酯(MEHP)与 5mdC/dG 呈正相关,MEHP 和 5mdC/dG 与脂联素呈负相关。研究发现,当 5mdC/dG 水平高于中位数时,MEHP 与脂联素之间的负相关更强。这一结果得到了非标准化回归系数的差异支持(-0.095 与-0.049,交互作用 P 值=0.038))。亚组分析还表明,在 ACE I/I 基因型个体中,MEHP 与脂联素呈负相关,但在其他基因型个体中无此相关性,尽管交互作用 P 值为边缘显著(0.06)。结构方程模型分析表明,MEHP 对脂联素有直接的负向影响,通过 5mdC/dG 也有间接影响。

结论

在这个年轻的台湾人群中,我们的发现表明,尿液 MEHP 水平与血清脂联素水平呈负相关,表观遗传修饰可能在这种关联中起作用。需要进一步研究来验证这些结果并确定因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b88/10189977/5b83bcd04f86/13148_2023_1502_Fig1_HTML.jpg

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