基于上海市同卵双生子的胰岛素抵抗与全基因组DNA甲基化关联研究  

A study on the association between insulin resistance and genome-wide DNA methylation based on Shanghai monozygotic twins

作　　者：冯静源 周荣飞 刘宏伟 胡子涵 吴非 王惠婷 岳俊宏 朱珍妮[2] 吴凡[1] Feng Jingyuan;Zhou Rongfei;Liu Hongwei;Hu Zihan;Wu Fei;Wang Huiting;Yue Junhong;Zhu Zhenni;Wu Fan(School of Public Health,Fudan University,Shanghai 200032,China;Shanghai Municipal Center for Disease Control and Prevention,Shanghai 200336,China)

机构地区：[1]复旦大学公共卫生学院,上海200032 [2]上海市疾病预防控制中心,上海200336

出　　处：《中华流行病学杂志》2024年第7期932-940,共9页Chinese Journal of Epidemiology

基　　金：国家重点研发计划(2022YFC3600801);上海市高水平地方高校建设项目(DGF201006-1/007)。

摘　　要：目的基于上海市双生子人群,探讨胰岛素抵抗(IR)与全基因组DNA甲基化之间的关联。方法于2012-2013、2017-2018和2022-2023年招募上海市成年同卵双生子(MZ)作为研究对象,通过问卷调查、体格测量和实验室检测收集相关信息,进行甲基化检测,采用广义线性混合效应模型分析单个位点DNA甲基化水平与稳态模型2胰岛素抵抗指数(HOMA2-IR)之间的关联,并采用非配对和配对设计分析DNA甲基化水平与IR表型之间的关联,对筛选出的阳性位点进行聚类分析得到位点簇,通过广义线性回归评估甲基化模式。结果本研究纳入100对MZ,发现cg10535199-2q23.1(β=0.74%,P=1.51×10^(-7),OR=1.06,95%CI:1.03~1.09)和ch.17.49619327-SPOP(β=0.23%,P=7.54×10^(-7),OR=1.17,95%CI:1.08~1.28)位点高甲基化超过有建议意义的关联水平,经多重比较校正后,未发现位点达到基因组显著性水平,配对分析结果无统计学意义。识别出2个HOMA2-IR位点簇,位点簇1甲基化下调(β=-0.39%,P<0.001),位点簇2甲基化上调(β=0.47%,P<0.001)。结论IR与DNA甲基化之间存在关联,遗传因素可能在关联中发挥作用。Objective To explore the association between insulin resistance(IR)and genome-wide DNA methylation based on Shanghai twin study.Methods Monozygotic twins(MZ)from Shanghai were recruited during 2012-2013,2017-2018,and 2022-2023.Data were collected by questionnaire survey,physical examination and laboratory tests.Genome-wide DNA methylation was quantified.Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance(HOMA2-IR).Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR.Cluster analysis was conducted to identify the clusters of top significant sites.Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results A total of 100 MZ pairs were included in this study.Hypermethylated cg10535199-2q23.1(β=0.74%,P=1.51×10^(-7),OR=1.06,95%CI:1.03-1.09)and ch.17.49619327-SPOP(β=0.23%,P=7.54×10^(-7),OR=1.17,95%CI:1.08-1.28)were identified with suggestive significance.After correcting for multiple testing,no sites reached genome-wide significance.There was no statistical significance in the paired analysis.Two clusters with hypomethylated(β=-0.39%,P<0.001)and hypermethylated(β=0.47%,P<0.001)patterns were observed for HOMA2-IR.Conclusions IR was significantly associated with DNA methylation,and genetic factors might contribute to the association.

关 键 词：双生子 胰岛素抵抗 糖尿病 DNA甲基化 表观遗传流行病学 关联研究 

分 类 号：R587.1[医药卫生—内分泌]