Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation.
Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation.
复制标题
DOI：
10.1016/j.metabol.2014.01.007
复制
发表时间：
2014-05
影响因子：
9.8
通讯作者：
Hanson, Robert L.
中科院分区：
文献类型：
--
作者：
del Rosario, Melissa C.;Ossowski, Vicky;Knowler, William C.;Bogardus, Clifton;Baier, Leslie J.;Hanson, Robert L.
本研究的目的是调查DNA甲基化在介导妊娠期糖尿病母亲的后代患2型糖尿病风险增加中的潜在作用。外周血白细胞采集自非糖尿病皮马印第安人，他们是糖尿病母亲的后代（ODM; n = 14）或非糖尿病母亲的后代（ONDM; n = 14）。两组在年龄、性别、母亲年龄和皮马族比例方面相匹配。使用MeDIP-芯片测定法在Affytelium Human Tiling 2.0R阵列上测定差异甲基化区域。使用基于模型的平铺阵列分析（MAT）算法分析数据，并且与推定的启动子重叠的4883个区域被鉴定为差异甲基化的，已经满足经验推导的阈值（标称p < 0.0077）。对具有差异甲基化启动子的基因列表进行KEGG途径分析以确定由这些基因富集的典型代谢途径。对具有差异甲基化启动子的基因的通路分析鉴定了前3个富集通路为年轻人成熟型糖尿病（MODY）、2型糖尿病和Notch信号传导。已知这些通路中的几个基因影响胰腺发育和胰岛素分泌。这些发现支持了这样的假设，即表观遗传变化可能通过影响妊娠期间患有糖尿病的母亲的后代的β细胞功能而增加2型糖尿病的风险。
The aim of this study is to investigate the potential role of DNA methylation in mediating the increased risk of developing type 2 diabetes in offspring of mothers who had diabetes during pregnancy. Peripheral blood leukocytes were collected from non-diabetic Pima Indians who were either offspring of diabetic mothers (ODM; n = 14) or offspring of nondiabetic mothers (ONDM; n = 14). The two groups were matched for age, sex, age of mother, and fraction of Pima ethnicity. Differentially methylated regions were determined using a MeDIP-chip assay on an Affymetrix Human Tiling 2.0R Array. Data were analyzed using the model based analysis of tiling arrays (MAT) algorithm, and 4883 regions overlapping with putative promoters, were identified as differentially methylated, having met an empirically derived threshold (nominal p < 0.0077). The list of genes with differentially methylated promoters were subjected to KEGG pathway analysis to determine canonical metabolic pathways enriched by these genes. Pathway analysis of genes with differentially methylated promoters identified the top 3 enriched pathways as maturity onset diabetes of the young (MODY), type 2 diabetes, and Notch signaling. Several genes in these pathways are known to affect pancreatic development and insulin secretion These findings support the hypothesis that epigenetic changes may increase the risk of type 2 diabetes via an effect on β-cell function in the offspring of mothers with diabetes during pregnancy.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点
影响因子：
30.8
作者：
Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
通讯作者：
Seielstad, Mark
影响因子：
7.7
作者：
Dabelea, D;Hanson, RL;Knowler, WC
通讯作者：
Knowler, WC
影响因子：
8.2
作者：
KNOWLER, WC;BENNETT, PH;DONIACH, D
通讯作者：
DONIACH, D
影响因子：
11.4
作者：
Volkmar, Michael;Dedeurwaerder, Sarah;Cunha, Daniel A.;Ndlovu, Matladi N.;Defrance, Matthieu;Deplus, Rachel;Calonne, Emilie;Volkmar, Ute;Igoillo-Esteve, Mariana;Naamane, Najib;Del Guerra, Silvia;Masini, Matilde;Bugliani, Marco;Marchetti, Piero;Cnop, Miriam;Eizirik, Decio L.;Fuks, Francois
通讯作者：
Fuks, Francois