Genome-Wide Placental Gene Methylations in Gestational Diabetes Mellitus, Fetal Growth and Metabolic Health Biomarkers in Cord Blood.
Genome-Wide Placental Gene Methylations in Gestational Diabetes Mellitus, Fetal Growth and Metabolic Health Biomarkers in Cord Blood.
复制标题
妊娠期糖尿病、胎儿生长和代谢健康中脐带血生物标志物的全基因组胎盘基因甲基化
DOI：
10.3389/fendo.2022.875180
复制
发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
妊娠期糖尿病(GDM)会增加后代患代谢综合征的风险。表观遗传改变是一种可疑的机制。在一些表观基因组范围的关联研究中，妊娠期糖尿病与胎盘DNA甲基化变化有关。目前尚不清楚哪些基因或途径受到影响，以及是否有任何胎盘差异基因甲基化与胎儿生长或循环代谢健康生物标志物相关。在一项表观基因组范围的关联研究中，我们使用Infinium MylationEPIC BeadChip，试图识别GDM中全基因组胎盘差异甲基化基因和丰富的途径，并评估它们与脐带血中胎儿生长和代谢健康生物标记物的相关性。研究样本为30对妊娠期糖尿病足月胎盘和正常血糖孕妇(对照组)，按婴儿性别和分娩时胎龄匹配。脐血代谢健康生物标志物包括胰岛素、C肽、胰岛素原、IGF-I、IGF-II、瘦素和脂联素。校正母亲年龄、孕前体重指数、产次、分娩方式和胎盘细胞类型异质性，在妊娠期糖尿病组和对照组之间共检测到256个差异甲基化位置(DMPS，130个高甲基化，126个低甲基化)，占多重测试的错误发现率和贝塔值差异的0.05。在位点和区域水平的分析中，WSCD2被鉴定为差异甲基化基因。我们验证了7个高甲基化基因(CYP1A2、GFRA1、HDAC4、LIMS2、NAV3、PAX6、UPK1B)和10个低甲基化基因(DPP10、CPLX1、CSMD2、GPR133、NRXN1、PCSK9、Penk、PRDM16、PTPRN2、TNXB)。我们没有发现任何丰富的途径，解释了多次测试。11个基因(CYP2D7P1、PCDHB15、ERG、SIRPB1、DKK2、RAPGEF5、CACNA2D4、PCSK9、TSNARE1、CADM2、KCNAB2)的DMPs与出生体重(z评分)相关。胎盘基因甲基化与脐血生物标志物之间无显著相关性。总而言之，妊娠期糖尿病与一些胎盘基因的DNA甲基化改变有关，但这些胎盘基因甲基化与脐血中观察到的代谢健康生物标记物(胎儿生长因子、瘦素和脂联素)无关。我们验证了GDM中17个差异甲基化的胎盘基因，并确定了11个与胎儿生长相关的差异甲基化基因。
Gestational diabetes mellitus (GDM) “program” an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.
登录
查看更多内容
影响因子：
4.8
作者：
Han, P;Werber, J;Michaeli, T
通讯作者：
Michaeli, T
影响因子：
2.1
作者：
Gao C;Hsu FC;Dimitrov LM;Okut H;Chen YI;Taylor KD;Rotter JI;Langefeld CD;Bowden DW;Palmer ND
通讯作者：
Palmer ND
影响因子：
3.6
作者：
Itoh, Nobuyuki
通讯作者：
Itoh, Nobuyuki
影响因子：
5.6
作者：
Gagne-Ouellet, Valerie;Breton, Edith;Bouchard, Luigi
通讯作者：
Bouchard, Luigi
影响因子：
3.8
作者：
Logue MW;Smith AK;Wolf EJ;Maniates H;Stone A;Schichman SA;McGlinchey RE;Milberg W;Miller MW
通讯作者：
Miller MW