Associations Between Paternally Transmitted Fetal <i>IGF2</i> Variants and Maternal Circulating Glucose Concentrations in Pregnancy

Petry, Clive J.; Seear, Rachel; Wingate, Dianne L.; Manico, Lucy; Acerini, Carlo L.; Ong, Ken K.; Hughes, Ieuan A.; Dunger, David B.

doi:10.2337/db11-0689

Cited by 32 publications

(49 citation statements)

References 40 publications

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“…We found that in a similar model in which phenotypically wild-type pregnant mice carrying litters where around half of the offspring had the H19 gene and the nearby Igf2 control element disrupted, hyperglycaemia and placentomegaly were evident in late pregnancy [67]. We then found similar associations between fetal IGF2 SNPs and maternal glucose concentrations in humans [68], raised glucose concentrations themselves being associated with an increased risk of developing preeclampsia [69].…”

Section: Animal Studiesmentioning

confidence: 51%

“…We suggested that fetal imprinted genes could influence the risk of the mother developing hypertensive disorders in pregnancy and gestational diabetes [5,109]. We have published data consistent with this in terms of raised maternal glucose concentrations in late pregnancy and fetal (paternally expressed) IGF2 in both mice [67] and humans [68]. Preliminary analyses of results from our Cambridge Baby Growth Study cohort suggest that maternal blood pressure will also be associated with polymorphic variation in various fetal imprinted genes.…”

Section: Fetal Imprinted Genesmentioning

confidence: 56%

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The potential impact of the fetal genotype on maternal blood pressure during pregnancy

Petry

Beardsall

2014

Journal of Hypertension

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The heritability of pregnancy-induced hypertension (encompassing both gestational hypertension and preeclampsia) is around 0.47, suggesting that there is a genetic component to its development. However, the maternal genetic risk variants discovered so far only account for a small proportion of the heritability. Other genetic variants that may affect maternal blood pressure in pregnancy arise from the fetal genome, for example wild-type pregnant mice carrying offspring with Cdkn1c or Stox1 disrupted develop hypertension and proteinuria. In humans, there is a higher risk for preeclampsia in women carrying fetuses with Beckwith-Wiedemann syndrome (including those fetuses with CDKN1C mutations) and a lower risk for women carrying babies with trisomy 21. Other risk may be associated with imprinted fetal growth genes and genes that are highly expressed in the placenta such as GCM1. This article reviews the current state of knowledge linking the fetal genotype with maternal blood pressure in pregnancy.

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Section: Animal Studiesmentioning

confidence: 51%

Section: Fetal Imprinted Genesmentioning

confidence: 56%

The potential impact of the fetal genotype on maternal blood pressure during pregnancy

Petry

Beardsall

2014

Journal of Hypertension

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“…Also, in an animal study by Petry et al (2010), maternal glucose concentrations in pregnant mice were elevated among women carrying pups with targeted disruption of maternally transmitted fetal H19 D13 , which implied that variable fetal IGF2 expression could affect risk for GDM. Moreover, in an epidemiological study among 1160 mother/partner/offspring trios from the UK, Petry et al found that polymorphic variations in the paternally transmitted fetal IGF2 genotype, but not the maternal or maternally transmitted fetal IGF2 genotypes, were associated with increased maternal glucose concentrations in pregnancy, which could potentially alter the risk of maternal GDM (Petry et al, 2011). These studies highlighted a potential role of the paternal and fetal genomes, in addition to the maternal genome itself, in maternal glucose homeostasis during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants and the risk of gestational diabetes mellitus: a systematic review

Zhang

Bao

Rong

et al. 2013

Human Reproduction Update

242

208

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background: Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.methods: Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.results: Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (230G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P , 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P ¼ 0.002) per T allele of rs12255372.conclusions: In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.

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“…In women with certain maternal gene polymorphisms, fetal sex influenced important parameters of maternal physiology during pregnancy, including those of the glucose metabolism [23][24][25]. Moreover, paternally transmitted gene variants of the fetal IGF2 gene (which encodes insulin-like growth factor-II) were associated with increased maternal glucose concentrations, thus potentially altering her risk of developing gestational diabetes mellitus [28].…”

Section: Fetal Metabolites Associated With Maternal Gdmmentioning

confidence: 99%

“…Other potentially contributing factors discussed in the literature include chronic low-grade inflammation [20], different genetic, epigenetic and non-genetic environmental factors including nutrition [21][22][23][24][25][26]. Moreover, fetal sex [23,27] and fetal genes [28] have been shown to correlate with maternal glucose concentrations during pregnancy and thus may modulate the risk for maternal GDM. However, it is not clear if the fetus can impact on the maternal organism in such a regulating manner.…”

Section: Introductionmentioning

confidence: 99%

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

Reichetzeder

Prehn

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal

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Associations Between Paternally Transmitted Fetal IGF2 Variants and Maternal Circulating Glucose Concentrations in Pregnancy

Cited by 32 publications

References 40 publications

The potential impact of the fetal genotype on maternal blood pressure during pregnancy

The potential impact of the fetal genotype on maternal blood pressure during pregnancy

Genetic variants and the risk of gestational diabetes mellitus: a systematic review

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

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