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Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.

Publication ,  Journal Article
Guo, C; Ludvik, AE; Arlotto, ME; Hayes, MG; Armstrong, LL; Scholtens, DM; Brown, CD; Newgard, CB; Becker, TC; Layden, BT; Lowe, WL; Reddy, TE
Published in: Nat Commun
February 4, 2015

Maternal glucose levels during pregnancy impact the developing fetus, affecting metabolic health both early and later on in life. Both genetic and environmental factors influence maternal metabolism, but little is known about the genetic mechanisms that alter glucose metabolism during pregnancy. Here, we report that haplotypes previously associated with gestational hyperglycaemia in the third trimester disrupt regulatory element activity and reduce expression of the nearby HKDC1 gene. We further find that experimentally reducing or increasing HKDC1 expression reduces or increases hexokinase activity, respectively, in multiple cellular models; in addition, purified HKDC1 protein has hexokinase activity in vitro. Together, these results suggest a novel mechanism of gestational glucose regulation in which the effects of genetic variants in multiple regulatory elements alter glucose homeostasis by coordinately reducing expression of the novel hexokinase HKDC1.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 4, 2015

Volume

6

Start / End Page

6069

Location

England

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Pregnancy
  • Hyperglycemia
  • Humans
  • Hexokinase
  • Hep G2 Cells
  • Haplotypes
  • Genotype
  • Genome-Wide Association Study
  • Female
 

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Guo, C., Ludvik, A. E., Arlotto, M. E., Hayes, M. G., Armstrong, L. L., Scholtens, D. M., … Reddy, T. E. (2015). Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun, 6, 6069. https://doi.org/10.1038/ncomms7069
Guo, Cong, Anton E. Ludvik, Michelle E. Arlotto, M Geoffrey Hayes, Loren L. Armstrong, Denise M. Scholtens, Christopher D. Brown, et al. “Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.Nat Commun 6 (February 4, 2015): 6069. https://doi.org/10.1038/ncomms7069.
Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, et al. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun. 2015 Feb 4;6:6069.
Guo, Cong, et al. “Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.Nat Commun, vol. 6, Feb. 2015, p. 6069. Pubmed, doi:10.1038/ncomms7069.
Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, Brown CD, Newgard CB, Becker TC, Layden BT, Lowe WL, Reddy TE. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun. 2015 Feb 4;6:6069.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 4, 2015

Volume

6

Start / End Page

6069

Location

England

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Pregnancy
  • Hyperglycemia
  • Humans
  • Hexokinase
  • Hep G2 Cells
  • Haplotypes
  • Genotype
  • Genome-Wide Association Study
  • Female