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2013 | 1 | 1-9
Tytuł artykułu

Exposure to Maternal Diabetes in Utero and DNA Methylation Patterns in the Offspring

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Perturbations in early life environments, including intrauterine exposure to maternal gestational diabetes (GDM), are hypothesized to lead to metabolic imprinting resulting in increased risk of cardiometabolic outcomes later in life. We aimed to 1) identify candidate genes and biological pathways associated with differentially methylated regions (DMRs) in relation to exposure to GDM in utero and, 2) using mediation analysis, more definitively investigate the potential for mediation of the effect of exposure to maternal diabetes in utero on cardiometabolic traits in childhood risk through our identified DMRs. Genome-wide methylation analysis of peripheral blood mononuclear cell’s DNA was conducted in 21 healthy children, ages 8-12 years. P-values from multiple linear regression analyses for >27,000 CpG sites were ranked to identify DMRs between the exposure groups. Among the top 10 ranked DMRs, we identified several genes, including NPR1, PANK1, SCAND1, and GJA4, which are known to be associated with cardiometabolic traits. Gene enrichment analysis of the top 84 genes, each with p<=0.005, identified the ubiquitin proteasome system (UPS) as the most enriched biological pathway (p = 0.07). The UPS pathway reflects biological processes known to be associated with endothelial function, inflammation, lipid metabolism, insulin resistance and b-cell apoptosis, whose derangements are central to the pathogenesis of cardiometabolic diseases. Increased methylation of PYGO1 and CLN8 had the greatest relative mediation effect (RME = 87%, p=0.005 and RME=50%, p=0.01) on the impact of exposure to maternal diabetes in utero on VCAM-1 levels in the offspring. Multiple candidate genes and the UPS were identified for future study as possible links between exposure to maternal gestational diabetes in utero and adverse cardiometabolic traits in the offspring. In particular, increased methylation of PYGO1 and CLN8 may be biological links between intrauterine exposure to maternal diabetes and significantly increased VCAM-1 levels in the offspring.
Wydawca

Czasopismo
Rocznik
Tom
1
Strony
1-9
Opis fizyczny
Daty
otrzymano
2012-12-12
zaakceptowano
2013-02-04
online
2013-03-08
Twórcy
autor
  • Department of Epidemiology,
    University of Colorado Anschutz Medical
    Campus, Aurora, Colorado, USA, nancy.west@ucdenver.edu
  • Department of Biostatistics
    and Informatics, University of Colorado
    Anschutz Medical Campus,
    Aurora, Colorado, USA
autor
  • Department of Epidemiology,
    University of Colorado Anschutz Medical
    Campus, Aurora, Colorado, USA
Bibliografia
  • Barker DJ. Fetal origins of coronary heart disease. BMJ1995;311(6998):171-4.
  • Clausen TD, Mathiesen ER, Hansen T, Pedersen O, JensenDM, Lauenborg J, et al. Overweight and the metabolicsyndrome in adult offspring of women with diet-treatedgestational diabetes mellitus or type 1 diabetes. J ClinEndocrinol Metab 2009;94(7):2464-70.[WoS][Crossref][PubMed]
  • Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes inpregnancy on offspring: follow-up research in the PimaIndians. J Matern Fetal Med 2000;9(1):83-8.[PubMed]
  • Waterland RA, Jirtle RL. Transposable elements: targets forearly nutritional effects on epigenetic gene regulation. MolCell Biol 2003;23(15):5293-300.[Crossref][PubMed]
  • Jones PA, Baylin SB. The fundamental role of epigeneticevents in cancer. Nat Rev Genet 2002;3(6):415-28.[PubMed]
  • Ehrlich M. Expression of various genes is controlled by DNAmethylation during mammalian development. J Cell Biochem2003;88(5):899-910.[Crossref]
  • Zhou FC, Chen Y, Love A. Cellular DNA methylation programduring neurulation and its alteration by alcohol exposure.Birth Defects Res A Clin Mol Teratol 2011;91(8):703-15.[PubMed][WoS][Crossref]
  • Crume TL, Ogden L, West NA, Vehik KS, Scherzinger A,Daniels S, et al. Association of exposure to diabetes in uterowith adiposity and fat distribution in a multiethnic populationof youth: the Exploring Perinatal Outcomes among Children(EPOCH) Study. Diabetologia 2011;54(1):87-92.[WoS][Crossref]
  • Classification and diagnosis of diabetes mellitus and othercategories of glucose intolerance. National Diabetes DataGroup. Diabetes 1979;28(12):1039-57.[PubMed]
  • Marshall WA, Tanner JM. Growth and physiologicaldevelopment during adolescence. Annu Rev Med1968;19:283-300.[Crossref][PubMed]
  • Mayer-Davis EJ, Nichols M, Liese AD, Bell RA, DabeleaDM, Johansen JM, et al. Dietary intake among youth withdiabetes: the SEARCH for Diabetes in Youth Study. J Am DietAssoc 2006;106(5):689-97.[Crossref]
  • Kann L, Kinchen SA, Williams BI, Ross JG, Lowry R,Grunbaum JA, et al. Youth risk behavior surveillance--United States, 1999. MMWR CDC Surveill Summ2000;49(5):1-32.
  • Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM,Guo SS, Wei R, et al. CDC growth charts: United States. AdvData 2000;(314):1-27.[PubMed]
  • Friedewald WT, Levy RI, Fredrickson DS. Estimation ofthe concentration of low-density lipoprotein cholesterol inplasma, without use of the preparative ultracentrifuge. ClinChem 1972;18(6):499-502.[PubMed]
  • David HA, Nagaraja, H.N. Order Statistics. 3rd ed. New York:Wiley; 2003.
  • Adkins RM, Thomas F, Tylavsky FA, Krushkal J. Parental agesand levels of DNA methylation in the newborn are correlated.BMC Med Genet 2011;12:47.[PubMed][WoS][Crossref]
  • Bryan AD, Magnan RE, Hooper AE, Harlaar N, Hutchison KE.Physical Activity and Differential Methylation of Breast CancerGenes Assayed from Saliva: A Preliminary Investigation. AnnBehav Med 2013;45(1):89-98.[Crossref][WoS][PubMed]
  • Dolinoy DC, Das R, Weidman JR, Jirtle RL. Metastableepialleles, imprinting, and the fetal origins of adult diseases.Pediatr Res 2007;61(5 Pt 2):30R-37R.[WoS][Crossref]
  • Ribaric S. Diet and aging. Oxid Med Cell Longev2012;2012:741468.[PubMed]
  • Huang da W, Sherman BT, Lempicki RA. Bioinformaticsenrichment tools: paths toward the comprehensive functionalanalysis of large gene lists. Nucleic Acids Res 2009;37(1):1-13.[Crossref][WoS]
  • Huang da W, Sherman BT, Lempicki RA. Systematicand integrative analysis of large gene lists using DAVIDbioinformatics resources. Nat Protoc 2009;4(1):44-57.[WoS]
  • Hosack DA, Dennis G, Jr., Sherman BT, Lane HC, LempickiRA. Identifying biological themes within lists of genes withEASE. Genome Biol 2003;4(10):R70.[PubMed]
  • Baron RM, Kenny DA. The moderator-mediator variabledistinction in social psychological research: conceptual,strategic, and statistical considerations. J Pers Soc Psychol[PubMed]
  • Freedman LS, Graubard BI, Schatzkin A. Statistical validationof intermediate endpoints for chronic diseases. Stat Med1992;11(2):167-78.[PubMed][Crossref]
  • Oliver PM, Fox JE, Kim R, Rockman HA, Kim HS, ReddickRL, et al. Hypertension, cardiac hypertrophy, and suddendeath in mice lacking natriuretic peptide receptor A. Proc NatlAcad Sci U S A 1997;94(26):14730-5.[Crossref]
  • Pitzalis MV, Sarzani R, Dessi-Fulgheri P, Iacoviello M,Forleo C, Lucarelli K, et al. Allelic variants of natriureticpeptide receptor genes are associated with family historyof hypertension and cardiovascular phenotype. J Hypertens2003;21(8):1491-6.[Crossref][PubMed]
  • Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S,Brodsky J, et al. Genome-wide association analysis ofmetabolic traits in a birth cohort from a founder population.Nat Genet 2009;41(1):35-46.[WoS][Crossref]
  • Lu Y, Dolle ME, Imholz S, van ‘t Slot R, Verschuren WM,Wijmenga C, et al. Multiple genetic variants along candidatepathways influence plasma high-density lipoproteincholesterol concentrations. J Lipid Res 2008;49(12):2582-9.[Crossref][WoS]
  • Babb R, Bowen BR. SDP1 is a peroxisome-proliferatoractivatedreceptor gamma 2 co-activator that binds throughits SCAN domain. Biochem J 2003;370(Pt 2):719-27.
  • Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H,Hirayama H, et al. Prediction of the risk of myocardialinfarction from polymorphisms in candidate genes. N Engl JMed 2002;347(24):1916-23.
  • Leu HB, Chung CM, Chuang SY, Bai CH, Chen JR, ChenJW, et al. Genetic variants of connexin37 are associated withcarotid intima-medial thickness and future onset of ischemicstroke. Atherosclerosis 2011;214(1):101-6.[PubMed][Crossref]
  • Stangl K, Stangl V. The ubiquitin-proteasome pathway andendothelial (dys)function. Cardiovasc Res 2010;85(2):281-90.[PubMed][Crossref]
  • Vieira O, Escargueil-Blanc I, Jurgens G, Borner C, AlmeidaL, Salvayre R, et al. Oxidized LDLs alter the activity of theubiquitin-proteasome pathway: potential role in oxidizedLDL-induced apoptosis. Faseb J 2000;14(3):532-42.[PubMed]
  • Willis MS, Townley-Tilson WH, Kang EY, Homeister JW,Patterson C. Sent to destroy: the ubiquitin proteasomesystem regulates cell signaling and protein quality controlin cardiovascular development and disease. Circ Res2010;106(3):463-78.[PubMed][Crossref][WoS]
  • Wing SS. The UPS in diabetes and obesity. BMC Biochem2008;9 Suppl 1:S6.[PubMed][WoS]
  • Rui L, Fisher TL, Thomas J, White MF. Regulation of insulin/insulin-like growth factor-1 signaling by proteasomemediateddegradation of insulin receptor substrate-2. J BiolChem 2001;276(43):40362-7.
  • Sun XJ, Goldberg JL, Qiao LY, Mitchell JJ. Insulin-inducedinsulin receptor substrate-1 degradation is mediatedby the proteasome degradation pathway. Diabetes1999;48(7):1359-64.[Crossref][PubMed]
  • Casas S, Gomis R, Gribble FM, Altirriba J, Knuutila S, Novials A.Impairment of the ubiquitin-proteasome pathway is a downstreamendoplasmic reticulum stress response induced by extracellularhuman islet amyloid polypeptide and contributes to pancreaticbeta-cell apoptosis. Diabetes 2007;56(9):2284-94.[PubMed][Crossref][WoS]
  • Berenson GS, Srnivasan SR. Cardiovascular risk factors inyouth with implications for aging: the Bogalusa Heart Study.Neurobiol Aging 2005;26(3):303-7.[Crossref][PubMed]
  • Hansson GK. Inflammation, atherosclerosis, and coronaryartery disease. N Engl J Med 2005;352(16):1685-95.
  • Zakynthinos E, Pappa N. Inflammatory biomarkers incoronary artery disease. J Cardiol 2009;53(3):317-33.[PubMed][Crossref]
  • West NA, Crume TL, Maligie MA, Dabelea D. Cardiovascularrisk factors in children exposed to maternal diabetes in utero.Diabetologia 2011;54(3):504-7.[PubMed][Crossref]
  • Fraser HB, Lam LL, Neumann SM, Kobor MS. Populationspecificityof human DNA methylation. Genome Biol2012;13(2):R8.[PubMed][Crossref]
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_2478_immun-2013-0001
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