An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth

被引:87
作者
Drake, Amanda J. [1 ]
McPherson, Rhoanne C. [1 ]
Godfrey, Keith M. [2 ,3 ,4 ]
Cooper, Cyrus [2 ]
Lillycrop, Karen A. [3 ,4 ]
Hanson, Mark A. [3 ,4 ]
Meehan, Richard R. [5 ,6 ]
Seckl, Jonathan R. [1 ]
Reynolds, Rebecca M. [1 ]
机构
[1] Univ Edinburgh, Queens Med Res Inst, Endocrinol Unit, Univ BHF Ctr Cardiovasc Sci, Edinburgh EH16 4TJ, Midlothian, Scotland
[2] Univ Southampton, Lifecourse Epidemiol Unit, Med Res Council, Southampton, Hants, England
[3] Univ Southampton, Southampton Gen Hosp, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England
[4] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
[5] Univ Edinburgh, Western Gen Hosp, IGMM, MRC Human Genet Unit, Edinburgh EH16 4TJ, Midlothian, Scotland
[6] Univ Edinburgh, Western Gen Hosp, Breakthrough Breast Canc Res Unit, Edinburgh EH16 4TJ, Midlothian, Scotland
关键词
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2; DNA METHYLATION; HYPOTHALAMIC PROOPIOMELANOCORTIN; PROMOTER METHYLATION; PRENATAL EXPOSURE; BIRTH-WEIGHT; RECEPTOR; EXPRESSION; PPARGC1A; ORIGINS;
D O I
10.1111/j.1365-2265.2012.04453.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective In epidemiological studies, adverse early-life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early-life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth. Design We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring. Measurements DNA methylation at 11 beta-hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA. Results Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy. Conclusions Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early-life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early-life maternal diet and/or foetal growth and cardiovascular disease risk in humans.
引用
收藏
页码:808 / 815
页数:8
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