DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial

被引：88

作者：

Cooper, Wendy N. ^{[2
]}

Khulan, Batbayar ^{[2
,3
]}

Owens, Stephen ^{[5
]}

Elks, Cathy E. ^{[6
]}

Seidel, Veronica ^{[2
]}

Prentice, Andrew M. ^{[5
]}

Belteki, Gusztav ^{[1
,7
]}

Ong, Ken K. ^{[1
,6
]}

Affara, Nabeel A. ^{[3
]}

Constancia, Miguel ^{[2
,4
,8
]}

Dunger, David B. ^{[1
,8
]}

机构：

[1] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England

[2] Univ Cambridge, Dept Obstet & Gynaecol, Metab Res Labs, Cambridge CB2 0QQ, England

[3] Univ Cambridge, Dept Pathol, Cambridge CB2 0QQ, England

[4] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 0QQ, England

[5] London Sch Hyg & Trop Med, Int Nutr Grp, MRC, London WC1, England

[6] Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England

[7] Cambridge Univ Hosp NHS Fdn Trust, Rosie Hosp, Neonatal Intens Care Unit, Cambridge, England

[8] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England

来源：

FASEB JOURNAL | 2012年 / 26卷 / 05期

基金：

英国生物技术与生命科学研究理事会;

关键词：

fetal programming; maternal nutrition; epigenetics; BECKWITH-WIEDEMANN-SYNDROME; PRENATAL EXPOSURE; SEASONAL-VARIATIONS; GENE-EXPRESSION; GAMBIAN WOMEN; DUTCH FAMINE; IGF2; GENE; GROWTH; DISEASE; MOUSE;

D O I：

10.1096/fj.11-192708

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a double-blind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.-Cooper, W. N., Khulan, B., Owens, S., Elks, C. E., Seidel, V., Prentice, A. M., Belteki, G., Ong, K. K., Affara, N. A., Constancia, M., Dunger, D. B. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 26, 1782-1790 (2012). www.fasebj.org

引用

页码：1782 / 1790

页数：9

共 35 条

[1]

Barker D.J., 1989, LANCET, V334, P577, DOI [10.1016/S0140-6736(89)90710-1, DOI 10.1016/S0140-6736(89)90710-1]

[2]

Barker D. J., 1986, LANCET, V327, P1077, DOI [10.1016/S0140-6736(86)91340-1, DOI 10.1016/S0140-6736(86)91340-1]

[3]

BATES CJ, 1994, EUR J CLIN NUTR, V48, P660

[4] SEASONAL-VARIATIONS IN PLASMA RETINOL AND CAROTENOID LEVELS IN RURAL GAMBIAN WOMEN [J].

BATES, CJ ;

VILLARD, L ;

PRENTICE, AM ;

PAUL, AA ;

WHITEHEAD, RG .

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1984, 78 (06) :814-817

[5] Sexual dimorphism in parental imprint ontogeny and contribution to embryonic development [J].

Bourc'his, Deborah ;

Proudhon, Charlotte .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2008, 282 (1-2) :87-94

[6] SEASONAL-VARIATION OF PEDIATRIC DISEASES IN THE GAMBIA, WEST-AFRICA [J].

BREWSTER, DR ;

GREENWOOD, BM .

ANNALS OF TROPICAL PAEDIATRICS, 1993, 13 (02) :133-146

[7] Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems [J].

Constância, M ;

Angiolini, E ;

Sandovici, I ;

Smith, P ;

Smith, R ;

Kelsey, G ;

Dean, W ;

Ferguson-Smith, A ;

Sibley, CP ;

Reik, W ;

Fowden, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (52) :19219-19224

[8] Does sex determination start at conception? [J].

Erickson, RP .

BIOESSAYS, 1997, 19 (11) :1027-1032

[9] Epigenetic differences arise during the lifetime of monozygotic twins [J].

Fraga, MF ;

Ballestar, E ;

Paz, MF ;

Ropero, S ;

Setien, F ;

Ballestart, ML ;

Heine-Suñer, D ;

Cigudosa, JC ;

Urioste, M ;

Benitez, J ;

Boix-Chornet, M ;

Sanchez-Aguilera, A ;

Ling, C ;

Carlsson, E ;

Poulsen, P ;

Vaag, A ;

Stephan, Z ;

Spector, TD ;

Wu, YZ ;

Plass, C ;

Esteller, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (30) :10604-10609

[10] An imprinted locus associated with transient neonatal diabetes mellitus [J].

Gardner, RJ ;

Mackay, DJG ;

Mungall, AJ ;

Polychronakos, C ;

Siebert, R ;

Shield, JPH ;

Temple, IK ;

Robinson, DO .

HUMAN MOLECULAR GENETICS, 2000, 9 (04) :589-596

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