Insulin-Like Growth Factor 2/H19 Methylation at Birth and Risk of Overweight and Obesity in Children

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• 作者：Ellen Perkins ; MD¹ ; Susan K. Murphy ; PhD² ; ³ ; Amy P. Murtha ; MD⁴ ; Joellen Schildkraut ; PhD¹ ; ⁵ ; Randy L. Jirtle ; PhD⁶ ; Wendy Demark-Wahnefried ; PhD⁸ ; Michele R. Forman ; PhD⁹ ; Joanne Kurtzberg ; MD⁷ ; Francine Overcash ; MPH¹ ; ⁵ ; Zhiqing Huang ; MD ; PhD² ; Cathrine Hoyo ; PhD¹ ; ^{cathrine.hoyo@duke.edu}
• 关键词：BMI ; Body mass index ; CpG ; Cytosine-phosphate-Guanine ; DMR ; Differentially methylated region ; IGF2 ; Insulin-like growth factor 2 ; NEST ; Newborn Epigenetics Study ; WFA ; Weight-for-age
• 刊名：The Journal of Pediatrics
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：161
• 期：1
• 页码：31-39
• 全文大小：157 K

文摘

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Objective

To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort.

Study design

Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ¡Ü85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity.

Results

The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7 % ; 95 % CI, 59.9 % -65.5 % ) than in infants with WFA ¡Ü85th percentile (59.3 % ; 95 % CI, 58.2 % -60.3 % ; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ¡Ü85th percentile and infants with WFA >85th percentile.

Conclusions

Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.