Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

Associations between the maternal circulating lipid profile in pregnancy and fetal imprinted gene alleles: a cohort study

Authors: Clive J. Petry, Albert Koulman, Liangjian Lu, Benjamin Jenkins, Samuel Furse, Philippa Prentice, Lee Matthews, Ieuan A. Hughes, Carlo L. Acerini, Ken K. Ong, David B. Dunger

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

Login to get access

Abstract

Background

Imprinted genes, which are expressed in a parent of origin-specific manner, are thought to mediate the genetic priorities of each parent in pregnancy. Recently we reported that some fetal imprinted gene variants are associated with maternal glucose concentrations and blood pressures in pregnancy. We suggest that the conflict between the effects of paternal and maternal transmitted genes starts at conception and may already be evident in measures of maternal metabolism in early pregnancy, before gestational diabetes is manifest.

Methods

Lipid fractions in maternal non-fasting serum collected around week 15 of pregnancy were profiled using direct infusion mass spectrometry in a subset Discovery Cohort (n = 200) of women from the Cambridge Baby Growth Study using direct infusion mass spectrometry. Associations between 151 haplotype-tag fetal polymorphisms in 16 imprinted genes and lipids were determined using partial least squares discriminant analysis. Variable importance in projection scores were used to identify those lipid species that contribute most to the underlying variation in the lipid profile and the concentrations of these species tested for associations with fetal imprinted gene alleles using linear regression. In an internal Validation Cohort (n = 567 women from the same cohort) the lipid fraction was profiled using liquid chromatography-mass spectrometry and tested for associations with the same fetal imprinted gene variants as above, followed by meta-analysis of associations from the Discovery and Validation Cohorts.

Results

The most significant associations were between a monounsaturated triglyceride (44:1) and both paternally-transmitted fetal H19 rs7950932 (R = 0.14, p = 2.9 × 10− 3, n = 386) and maternally-transmitted fetal FAM99A rs7131362 (R = 0.18, p = 6.2 × 10− 3, n = 351; association with maternal-untransmitted allele R = 0.08, p = 0.07, n = 328). This same triglyceride isoform was also associated with subsequent week 28 fasting glucose concentrations (R = 0.09, p = 9.9 × 10− 3, n = 673) and homeostasis model assessment of insulin resistance (R = 0.09, p = 0.01, n = 664).

Conclusions

Fetal imprinted genes may influence maternal circulating clinically relevant triglyceride concentrations early in pregnancy.
Literature
1.
Haig D, Westoby M. Parent-specific gene expression and the triploid endosperm. Am Nat. 1989;134:147–55.CrossRef
2.
3.
Reik W, Constância M, Fowden A, Anderson N, Dean W, Ferguson-Smith A, et al. Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J Physiol. 2003;547:35–44.CrossRefPubMedPubMedCentral
4.
Haig D. Placental hormones, genomic imprinting, and maternal–foetal communication. J Evol Biol. 1996;9:357–80.CrossRef
5.
Petry CJ, Ong KK, Dunger DB. Does the foetal genotype affect maternal physiology during pregnancy? Trends Mol Med. 2007;13:414–21.CrossRefPubMed
6.
Petry CJ, Beardsall K, Dunger DB. The potential impact of the foetal genotype on maternal blood pressure during pregnancy. J Hypertens. 2014;32:1553–61.CrossRefPubMed
7.
Petry CJ, Evans ML, Wingate DL, Ong KK, Reik W, Constância M, et al. Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13. Diabetes. 2010;59:282–6.CrossRefPubMed
8.
Petry CJ, Seear RV, Wingate DL, Manico L, Acerini CL, Ong KK, et al. Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy. Diabetes. 2011;60:3090–6.CrossRefPubMedPubMedCentral
9.
Petry CJ, Mooslehner K, Prentice P, Hayes MG, Nodzenski M, Scholtens DM, Hughes IA, Acerini CL, Ong KK, Lowe WL Jr, Dunger DB. Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations. Diabetes Metab. 2017;43:323–31.CrossRefPubMedPubMedCentral
10.
Petry CJ, Sanz Marcos N, Pimentel G, Hayes MG, Nodzenski M, Scholtens DM, et al. Associations between fetal imprinted genes and maternal blood pressure in pregnancy. Hypertension. 2016;68:1459–66.CrossRefPubMedPubMedCentral
11.
Simopoulos AP. Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk. Exp Biol Med (Maywood). 2010;235:785–95.CrossRef
12.
Lattka E, Koletzko B, Zeilinger S, Hibbeln JR, Klopp N, Ring SM, et al. Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon longitudinal study of parents and children (ALSPAC). Br J Nutr. 2013;109:1196–210.CrossRefPubMed
13.
Ghio A, Bertolotto A, Resi V, Volpe L, Di Cianni G. Triglyceride metabolism in pregnancy. Adv Clin Chem. 2011;55:133–53.CrossRefPubMed
14.
Schaefer-Graf UM, Graf K, Kulbacka I, Kjos SL, Dudenhausen J, Vetter K, et al. Maternal lipids as strong determinants of foetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care. 2008;31:1858–63.CrossRefPubMedPubMedCentral
15.
Vrijkotte TG, Krukziener N, Hutten BA, Vollebregt KC, van Eijsden M, Twickler MB. Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study. J Clin Endocrinol Metab. 2012;97:3917–25.CrossRefPubMed
16.
Petry CJ, Seear RV, Wingate DL, Acerini CL, Ong KK, Hughes IA, et al. Maternally transmitted foetal H19 variants and associations with birth weight. Hum Genet. 2011;130:663–70.CrossRefPubMed
17.
18.
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMed
19.
Rodríguez S, Gaunt TR, O’Dell SD, Chen XH, Gu D, Hawe E, et al. Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits. Hum Mol Genet. 2004;13:715–25.CrossRefPubMed
20.
Koulman A, Prentice P, Wong MC, Matthews L, Bond NJ, Eiden M, et al. The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism. Metabolomics. 2014;10:1018–25.CrossRefPubMedPubMedCentral
21.
Prentice P, Koulman A, Matthews L, Acerini CL, Ong KK, Dunger DB. Lipidomic analyses, breast- and formula-feeding, and growth in infants. J Pediatr. 2015;166:276–81.CrossRefPubMedPubMedCentral
22.
Graessler J, Schwudke D, Schwarz PE, Herzog R, Shevchenko A, Bornstein SR. Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS One. 2009;4:e6261.CrossRefPubMedPubMedCentral
23.
Lu L, Koulman A, Petry CJ, Jenkins B, Matthews L, Hughes IA, et al. An unbiased lipidomics approach identifies early second trimester lipids predictive of maternal glycemic traits and gestational diabetes mellitus. Diabetes Care. 2016;39:2232–9.CrossRefPubMedPubMedCentral
24.
Koulman A, Woffendin G, Narayana VK, Welchman H, Crone C, Volmer DA. High-resolution extracted ion chromatography, a new tool for metabolomics and lipidomics using a second-generation orbitrap mass spectrometer. Rapid Commun Mass Spectrom. 2009;23:1411–8.CrossRefPubMedPubMedCentral
25.
Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21:2191–2.CrossRefPubMed
26.
27.
Schulze R. Meta-analysis: a comparison of approaches. Cambridge, MA: Hogrefe & Huber Pub; 2004.
28.
Rice F, Thapar A. Estimating the relative contributions of maternal genetic, paternal genetic and intrauterine factors to offspring birth weight and head circumference. Early Hum Dev. 2010;86:425–32.CrossRefPubMedPubMedCentral
29.
Roberts LD, Murray AJ, Menassa D, Ashmore T, Nicholls AW, Griffin JL. The contrasting roles of PPARδ and PPARγ in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue. Genome Biol. 2011;12:R75.CrossRefPubMedPubMedCentral
30.
Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, et al. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011;121:1402–11.CrossRefPubMedPubMedCentral
31.
Lustig O, Ariel I, Ilan J, Lev-Lehman E, De-Groot N, Hochberg A. Expression of the imprinted gene H19 in the human fetus. Mol Reprod Dev. 1994;38:239–46.CrossRefPubMed
32.
Sandovici I, Kassovska-Bratinova S, Vaughan JE, Stewart R, Leppert M, Sapienza C. Human imprinted chromosomal regions are historical hot-spots of recombination. PLoS Genet. 2006;2:e101.CrossRefPubMedPubMedCentral
33.
Vu TH, Li T, Nguyen D, Nguyen BT, Yao XM, Hu JF, Hoffman AR. Symmetric and asymmetric DNA methylation in the human IGF2-H19 imprinted region. Genomics. 2000;64:132–43.CrossRefPubMed
34.
Smith AC, Choufani S, Ferreira JC, Weksberg R. Growth regulation, imprinted genes, and chromosome 11p15.5. Pediatr Res. 2007;61:43R–7R.CrossRefPubMed
35.
1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef
36.
Kong A, Steinthorsdottir V, Masson G, Thorleifsson G, Sulem P, Besenbacher S, et al. Parental origin of sequence variants associated with complex diseases. Nature. 2009;462:868–74.CrossRefPubMedPubMedCentral
37.
Petry CJ. Genetic risk factors for gestational diabetes. In: Petry CJ, editor. Gestational diabetes: origins, complications and treatment. Boca Raton, Florida, U.S.A.: CRC Press; 2014. p. 69–94.CrossRef
Metadata
Title
Associations between the maternal circulating lipid profile in pregnancy and fetal imprinted gene alleles: a cohort study
Authors
Clive J. Petry
Albert Koulman
Liangjian Lu
Benjamin Jenkins
Samuel Furse
Philippa Prentice
Lee Matthews
Ieuan A. Hughes
Carlo L. Acerini
Ken K. Ong
David B. Dunger
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-018-0399-x

Other articles of this Issue 1/2018

Reproductive Biology and Endocrinology 1/2018 Go to the issue

Research

Trophoblast differentiation, invasion and hormone secretion in a three-dimensional in vitro implantation model with rhesus monkey embryos

Research

Meta-analysis of ART outcomes in women with different preconception TSH levels

Review

Obesity as disruptor of the female fertility

Research

ART manipulation after controlled ovarian stimulation may not increase the risk of abnormal expression and DNA methylation at some CpG sites of H19,IGF2 and SNRPN in foetuses: a pilot study

Review

Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation

Hypothesis

Navigation problems of ICSI or naive blastocyst can be solved with artificial blastocyst