Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Dec;68(6):1459-1466.
doi: 10.1161/HYPERTENSIONAHA.116.08261. Epub 2016 Oct 24.

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy

Affiliations
Review

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy

Clive J Petry et al. Hypertension. 2016 Dec.

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.

Keywords: blood pressure; hypertension, pregnancy-induced; meta-analysis; placenta; preeclampsia.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest/Disclosures None.

Figures

Figure 1
Figure 1
Scatter diagram showing the association between the composite fetal imprinted gene allele score and the mean arterial blood pressure (A) around week 12 of pregnancy and (B) in the final two weeks of pregnancy. The regression lines with their shaded 95% confidence intervals are shown.

Similar articles

  • Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations.
    Petry CJ, Mooslehner K, Prentice P, Hayes MG, Nodzenski M, Scholtens DM, Hughes IA, Acerini CL, Ong KK, Lowe WL Jr, Dunger DB. Petry CJ, et al. Diabetes Metab. 2017 Sep;43(4):323-331. doi: 10.1016/j.diabet.2017.03.002. Epub 2017 Apr 6. Diabetes Metab. 2017. PMID: 28392167 Free PMC article.
  • Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion.
    Petry CJ, Burling KA, Barker P, Hughes IA, Ong KK, Dunger DB. Petry CJ, et al. J Clin Endocrinol Metab. 2021 May 13;106(6):e2413-e2422. doi: 10.1210/clinem/dgab123. J Clin Endocrinol Metab. 2021. PMID: 33640968 Free PMC article.
  • Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.
    Vidal AC, Murphy SK, Murtha AP, Schildkraut JM, Soubry A, Huang Z, Neelon SE, Fuemmeler B, Iversen E, Wang F, Kurtzberg J, Jirtle RL, Hoyo C. Vidal AC, et al. Int J Obes (Lond). 2013 Jul;37(7):907-13. doi: 10.1038/ijo.2013.47. Epub 2013 Mar 28. Int J Obes (Lond). 2013. PMID: 23609933 Free PMC article.
  • Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns.
    Kazmi N, Sharp GC, Reese SE, Vehmeijer FO, Lahti J, Page CM, Zhang W, Rifas-Shiman SL, Rezwan FI, Simpkin AJ, Burrows K, Richardson TG, Santos Ferreira DL, Fraser A, Harmon QE, Zhao S, Jaddoe VWV, Czamara D, Binder EB, Magnus MC, Håberg SE, Nystad W, Nohr EA, Starling AP, Kechris KJ, Yang IV, DeMeo DL, Litonjua AA, Baccarelli A, Oken E, Holloway JW, Karmaus W, Arshad SH, Dabelea D, Sørensen TIA, Laivuori H, Raikkonen K, Felix JF, London SJ, Hivert MF, Gaunt TR, Lawlor DA, Relton CL. Kazmi N, et al. Hypertension. 2019 Aug;74(2):375-383. doi: 10.1161/HYPERTENSIONAHA.119.12634. Epub 2019 Jun 24. Hypertension. 2019. PMID: 31230546 Free PMC article. Review.
  • The role and interaction of imprinted genes in human fetal growth.
    Moore GE, Ishida M, Demetriou C, Al-Olabi L, Leon LJ, Thomas AC, Abu-Amero S, Frost JM, Stafford JL, Chaoqun Y, Duncan AJ, Baigel R, Brimioulle M, Iglesias-Platas I, Apostolidou S, Aggarwal R, Whittaker JC, Syngelaki A, Nicolaides KH, Regan L, Monk D, Stanier P. Moore GE, et al. Philos Trans R Soc Lond B Biol Sci. 2015 Mar 5;370(1663):20140074. doi: 10.1098/rstb.2014.0074. Philos Trans R Soc Lond B Biol Sci. 2015. PMID: 25602077 Free PMC article. Review.

Cited by

References

    1. Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet. 2000;91:256–260. - PubMed
    1. Williams PJ, Broughton Pipkin F. The genetics of pre-eclampsia and other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:405–417. - PMC - PubMed
    1. Basson J, Simino J, Rao DC. Between candidate genes and whole genomes: time for alternative approaches in blood pressure genetics. Curr Hypertens Rep. 2012;14:46–61. - PMC - PubMed
    1. Laivuori H. Pitfalls in setting up genetic studies on preeclampsia. Pregnancy Hypertens. 2013;3:60. - PubMed
    1. Padmanabhan S, Caulfield M, Dominiczak AF. Genetic and molecular aspects of hypertension. Circ Res. 2015;116:937–959. - PubMed

MeSH terms