Oelsner Kathryn Tully, Guo Yan, To Sophie Bao-Chieu, Non Amy L, Barkin Shari L
College of Medicine, Medical University of South Carolina, 96 Jonathan Lucas St, Suite 601, MSC 617, Charleston, SC, 29425, USA.
Center for Quantitative Research, School of Medicine, Vanderbilt University, 2220 Pierce Ave, 571 Preston Research Building, Nashville, TN, USA.
BMC Genomics. 2017 Jan 9;18(1):57. doi: 10.1186/s12864-016-3473-9.
The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity.
Genome-wide DNA methylation was conducted on 92 saliva samples collected from Hispanic preschool children using the Infinium Illumina HumanMethylation 450 K BeadChip (Illumina, San Diego, CA, USA), which interrogates >484,000 CpG sites associated with ~24,000 genes. The analysis was limited to 936 genes that have been associated with obesity in a prior GWAS Study. Child DNA methylation at 17 CpG sites was found to be significantly associated with maternal BMI, with increased methylation at 12 CpG sites and decreased methylation at 5 CpG sites. Pathway analysis revealed methylation at these sites related to homocysteine and methionine degradation as well as cysteine biosynthesis and circadian rhythm. Furthermore, eight of the 17 CpG sites reside in genes (FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1) that have prior known associations with obesity, diabetes, and the insulin pathway.
Our study confirms that saliva is a practical human tissue to obtain in community settings and in pediatric populations. These salivary findings indicate potential epigenetic differences in Hispanic preschool children at risk for pediatric obesity. Identifying early biomarkers and understanding pathways that are epigenetically regulated during this critical stage of child development may present an opportunity for prevention or early intervention for addressing childhood obesity.
The clinical trial protocol is available at ClinicalTrials.gov ( NCT01316653 ). Registered 3 March 2011.
表观遗传过程和机制的研究提供了一种动态方法，用于评估肥胖易感性方面复杂的个体差异。然而，尽管这个发育阶段与体重增加轨迹相关，但很少有研究调查肥胖高危学龄前儿童的表观遗传模式。我们假设西班牙裔儿童中关键致肥胖基因的唾液DNA甲基化模式将：1）与母亲的体重指数相关；2）有助于识别与肥胖高危儿童相关的途径。
使用Illumina HumanMethylation 450K BeadChip（Illumina，美国加利福尼亚州圣地亚哥）对从西班牙裔学龄前儿童收集的92份唾液样本进行全基因组DNA甲基化检测，该芯片可检测与约24,000个基因相关的超过484,000个CpG位点。分析限于先前全基因组关联研究中与肥胖相关的936个基因。发现17个CpG位点的儿童DNA甲基化与母亲的体重指数显著相关，其中12个CpG位点甲基化增加，5个CpG位点甲基化减少。通路分析显示这些位点的甲基化与同型半胱氨酸和蛋氨酸降解以及半胱氨酸生物合成和昼夜节律有关。此外，17个CpG位点中的8个位于先前已知与肥胖、糖尿病和胰岛素途径相关的基因（FSTL1、SORCS2、NRF1、DLC1、PPARGC1B、CHN2、NXPH1）中。
我们的研究证实，唾液是在社区环境和儿科人群中获取的实用人体组织。这些唾液检测结果表明，西班牙裔肥胖高危学龄前儿童存在潜在的表观遗传差异。在儿童发育的这个关键阶段识别早期生物标志物并了解表观遗传调控的途径，可能为预防或早期干预儿童肥胖提供机会。
临床试验方案可在ClinicalTrials.gov上获取（NCT01316653）。于2011年3月3日注册。
