Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight

被引:82
|
作者
Hoyo, Cathrine [1 ,2 ,3 ]
Fortner, Kimberly [4 ]
Murtha, Amy P. [4 ]
Schildkraut, Joellen M. [2 ,3 ]
Soubry, Adelheid [3 ]
Demark-Wahnefried, Wendy [5 ]
Jirtle, Randy L. [6 ]
Kurtzberg, Joanne [7 ]
Forman, Michele R. [8 ]
Overcash, Francine [2 ]
Huang, Zhiqing [9 ,10 ]
Murphy, Susan K. [3 ,9 ,10 ]
机构
[1] Duke Univ, Sch Med, Div Clin Epidemiol, Dept Obstet & Gynecol, Durham, NC 27705 USA
[2] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27705 USA
[3] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Durham, NC 27710 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA
[6] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA
[7] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27705 USA
[8] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
[9] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC 27708 USA
[10] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27708 USA
关键词
IGF2; H19; ELISA; DNA methylation; Epigenetics; Epidemiology; FACTOR-II GENE; CTCF-BINDING SITES; BREAST-CANCER RISK; FOLIC-ACID USE; COLORECTAL-CANCER; PROSTATE-CANCER; DNA-METHYLATION; ALTERED METHYLATION; TEMPORAL STABILITY; OVARIAN-CANCER;
D O I
10.1007/s10552-012-9932-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. hods Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Results Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (beta = -9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI >30 kg/m(2), beta = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Conclusion Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.
引用
收藏
页码:635 / 645
页数:11
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