DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
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DOI：
10.1186/s13148-021-01213-3
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发表时间：
2022-01-09
影响因子：
5.7
通讯作者：
EMPHASIS study group
中科院分区：
文献类型：
--
作者：
Antoun E;Issarapu P;di Gravio C;Shrestha S;Betts M;Saffari A;Sahariah SA;Sankareswaran A;Arumalla M;Prentice AM;Fall CHD;Silver MJ;Chandak GR;Lillycrop KA;EMPHASIS study group
心脏代谢性疾病(CMD)的患病率正在全球范围内上升，环境诱导的表观遗传变化被认为起到了一定作用。很少有研究调查低收入和中等收入国家儿童的表观遗传学与CMD风险因素的关系。我们试图在印度和冈比亚的儿童中确定DNA甲基化(DNaM)和CMD危险因素之间的联系。我们使用Illumina InfiniumHumanMALIZATION 850/K珠芯片阵列，询问了293名冈比亚(7-9岁)和698名印度(5-7岁)儿童的dNaM。我们在冈比亚儿童中发现差异甲基化CPGS(DmCpGs)与收缩压、空腹胰岛素、甘油三酯和低密度脂蛋白-胆固醇有关；在印度儿童中发现与胰岛素敏感性、胰岛素生成指数和高密度脂蛋白-胆固醇相关。队列之间的dmCpg没有重叠。Meta分析发现与胰岛素分泌和脉压相关的dmCpg不同于队列特有的dmCpg。几个不同的甲基化区域与舒张压、胰岛素敏感性和空腹血糖相关，但这些区域与dmCpGs不重叠。我们在冈比亚人的三个与低密度脂蛋白相关的dmCGG上发现了显著的顺式甲基QTL；然而，甲基化并不能调节基因对CMD结果的影响。这项研究确定了与印度和冈比亚儿童不同的dNaM相关的心脏代谢生物标志物。大多数关联是特定于队列的，可能反映了环境和种族的差异。网上版载有补充材料，可在10.1186/s13148021-01213-3查阅。
The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and CMD risk factors in children from India and The Gambia. Using the Illumina Infinium HumanMethylation 850 K Beadchip array, we interrogated DNAm in 293 Gambian (7–9 years) and 698 Indian (5–7 years) children. We identified differentially methylated CpGs (dmCpGs) associated with systolic blood pressure, fasting insulin, triglycerides and LDL-Cholesterol in the Gambian children; and with insulin sensitivity, insulinogenic index and HDL-Cholesterol in the Indian children. There was no overlap of the dmCpGs between the cohorts. Meta-analysis identified dmCpGs associated with insulin secretion and pulse pressure that were different from cohort-specific dmCpGs. Several differentially methylated regions were associated with diastolic blood pressure, insulin sensitivity and fasting glucose, but these did not overlap with the dmCpGs. We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes. This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children. Most associations were cohort specific, potentially reflecting environmental and ethnic differences. The online version contains supplementary material available at 10.1186/s13148-021-01213-3.
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