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Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy.

ABSTRACT: In addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1160 DNA trios from 2 established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies) and seek replication in 1367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant univariate associations, all independent of fetal sex, were observed in the Cambridge cohorts, including FAM99A rs1489945 transmitted from the mother (P=2×10-4), DLK1 rs10139403 (mother; P=9×10-4), DLK1 rs12147008 (mother; P=1×10-3), H19 rs217222 (father; P=1×10-3), SNRPN rs1453556 (father; P=1×10-3), IGF2 rs6356 (father; P=1×10-3), and NNAT rs6066671 (father; P=1×10-3). In meta-analysis including additional independent Hyperglycemia and Adverse Pregnancy Outcome Study data, the association with maternally transmitted fetal DLK1 rs10139403 reached genome-wide significance (P=6.3×10-10). With the exception of fetal rs1489945 and rs217222, all of other associations were unidirectional and most were statistically significant. To further explore the significance of these relationships, we developed an allele score based on the univariate findings. The score was strongly associated with maternal blood pressure at 31 weeks (P=4.1×10-8; adjusted r2=5.6%) and 37 weeks of pregnancy (P=1.1×10-4; r2=3.6%), and during the last 2 weeks before parturition (P=1.1×10-10; r2=8.7%). It was also associated with gestational hypertension (odds ratio, 1.54 [range, 1.14-2.09] per allele; P=0.005; 45 cases and 549 controls). These data support the concept that fetal imprinted genes are related to the development of gestational hypertension.

SUBMITTER: Petry CJ

PROVIDER: S-EPMC5159231 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy.

Petry Clive J CJ Sanz Marcos Nuria N Pimentel Gracielle G Hayes M Geoffrey MG Nodzenski Michael M Scholtens Denise M DM Hughes Ieuan A IA Acerini Carlo L CL Ong Ken K KK Lowe William L WL Dunger David B DB

Hypertension (Dallas, Tex. : 1979) 20161024 6

In addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1160 DNA trios from 2 established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies) and seek replication in 1367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant uni ...[more]

PMID: 27777362

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Project description: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.

Dataset Information

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy.

Publications

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy.

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