Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Cong Guo, Anton E. Ludvik, Michelle E. Arlotto, M. Geoffrey Hayes, Loren L. Armstrong, Denise M. Scholtens, Christopher D. Brown, Christopher B. Newgard, Thomas C. Becker, Brian T. Layden, William L. Lowe, Timothy E. Reddy

ABSTRACT

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. More... »

PAGES

6069

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms7069

DOI

http://dx.doi.org/10.1038/ncomms7069

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018393328

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25648650


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