BACKGROUND Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. METHODS Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. RESULTS Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22. CONCLUSIONS The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.

中文翻译：

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母亲糖尿病和肥胖会影响大部分西班牙裔人群的胎儿表观基因组。

背景技术肥胖和糖尿病与成人以及肥胖和糖尿病母亲的后代的许多不良健康后果直接相关。西班牙裔美国人特别容易患肥胖症、糖尿病和终末期肾病。通过产前编程导致的母亲肥胖和/或糖尿病可能会改变胎儿的表观基因组，增加其后代患代谢性疾病的风险。本研究的目的是确定怀孕期间的母亲肥胖或糖尿病是否会导致 CpG 岛的婴儿甲基化发生变化，该岛与特定于肥胖或糖尿病疾病途径的目标基因相邻，主要是西班牙裔人群。方法 使用 Illumina Infinium MethylationEPIC BeadChip 测定 69 名新生儿脐带血中的甲基化水平。超过850，分析了 000 个不同的探针位点以确定母亲肥胖和/或糖尿病是否直接归因于差异甲基化；对重要的 CpG 位点进行了表观基因组范围和区域分析。结果 在质量控制之后，分析了来自 69 名新生儿（23 名正常足月 (NT)、14 名糖尿病 (DM)、23 名肥胖 (OB)、9 名 DM/OB）的无颗粒白细胞样本的超过 850,000 个不同的探针位点。考虑了 NT、DM、OB 和 DM/OB 之间的对比。在多次测试校正后，15 个 CpG 显示出来自 NT 的差异甲基化，与糖尿病和非糖尿病亚组之间的 10 个差异甲基化基因 CCDC110、KALRN、PAG1、GNRH1、SLC2A9、CSRP2BP、HIVEP1、RALGDS、DHX37 和 SCNN1D 相关. 糖尿病的影响部分是由 HOOK2、LCE3C、和TMEM63B。肥胖的影响部分是由 LTF 和 DUSP22 的差异甲基化介导的。结论 所提供的数据突出了可能由母体糖尿病和/或肥胖介导的相关甲基化模式改变。需要更大规模的研究来调查已识别的差异甲基化基因座的作用以及对新生儿身体成分和代谢疾病未来健康风险因素的影响。未来的其他考虑应针对西班牙裔继承的作用。跨代繁殖和发育规划的潜在未来目标可能会降低人口肥胖和糖尿病风险。结论 所提供的数据突出了可能由母体糖尿病和/或肥胖介导的相关甲基化模式改变。需要更大规模的研究来调查已识别的差异甲基化基因座的作用以及对新生儿身体成分和代谢疾病未来健康风险因素的影响。未来的其他考虑应针对西班牙裔继承的作用。跨代繁殖和发育规划的潜在未来目标可能会降低人口肥胖和糖尿病风险。结论 所提供的数据突出了可能由母体糖尿病和/或肥胖介导的相关甲基化模式改变。需要更大规模的研究来调查已识别的差异甲基化基因座的作用以及对新生儿身体成分和代谢疾病未来健康风险因素的影响。未来的其他考虑应针对西班牙裔继承的作用。跨代繁殖和发育规划的潜在未来目标可能会降低人口肥胖和糖尿病风险。未来的其他考虑应针对西班牙裔继承的作用。跨代繁殖和发育规划的潜在未来目标可能会降低人口肥胖和糖尿病风险。未来的其他考虑应针对西班牙裔继承的作用。跨代繁殖和发育规划的潜在未来目标可能会降低人口肥胖和糖尿病风险。