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GCKR : How genetic variation across the allelic spectrum influences protein function and metabolic traits in humans

Orho-Melander, Marju LU and Gloyn, Anna L. (2016) In The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation p.317-336
Abstract

Genome-wide association studies (GWAS) have generated considerable interest in glucokinase regulatory protein (GKRP; gene name GCKR) which is an inhibitor of hepatic glucokinase (GCK), an enzyme that plays a critical role in glucose update and disposal in liver. From the initial discovery of GCKR variants associated with triglyceride and glucose levels through the identification of pleiotropic associations with a wide variety of metabolic phenotypes, we have learned a great deal about the importance of GKRP as a critical node in hepatic metabolism. GKRP remains one of the few well-studied GWAS loci where attempts have been made to understand the functional as well as the phenotypic impact of genetic variants across the allelic spectrum.... (More)

Genome-wide association studies (GWAS) have generated considerable interest in glucokinase regulatory protein (GKRP; gene name GCKR) which is an inhibitor of hepatic glucokinase (GCK), an enzyme that plays a critical role in glucose update and disposal in liver. From the initial discovery of GCKR variants associated with triglyceride and glucose levels through the identification of pleiotropic associations with a wide variety of metabolic phenotypes, we have learned a great deal about the importance of GKRP as a critical node in hepatic metabolism. GKRP remains one of the few well-studied GWAS loci where attempts have been made to understand the functional as well as the phenotypic impact of genetic variants across the allelic spectrum. Given the interest in developing liver-specific glucokinase activators and small molecules which disrupt the GKRP:GCK interaction for the treatment of type 2 diabetes, these genetic insights provide a wealth of information regarding efficacy and potential adverse on-target effects in humans.

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author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
in
The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation
pages
20 pages
publisher
Springer International Publishing
external identifiers
  • Scopus:84978267545
ISBN
9783319015743
9783319015736
DOI
10.1007/978-3-319-01574-3_15
language
English
LU publication?
yes
id
7bd20bcb-9329-4fda-8f19-81f45abe5600
date added to LUP
2016-07-25 12:58:13
date last changed
2016-10-27 08:55:56
@misc{7bd20bcb-9329-4fda-8f19-81f45abe5600,
  abstract     = {<p>Genome-wide association studies (GWAS) have generated considerable interest in glucokinase regulatory protein (GKRP; gene name GCKR) which is an inhibitor of hepatic glucokinase (GCK), an enzyme that plays a critical role in glucose update and disposal in liver. From the initial discovery of GCKR variants associated with triglyceride and glucose levels through the identification of pleiotropic associations with a wide variety of metabolic phenotypes, we have learned a great deal about the importance of GKRP as a critical node in hepatic metabolism. GKRP remains one of the few well-studied GWAS loci where attempts have been made to understand the functional as well as the phenotypic impact of genetic variants across the allelic spectrum. Given the interest in developing liver-specific glucokinase activators and small molecules which disrupt the GKRP:GCK interaction for the treatment of type 2 diabetes, these genetic insights provide a wealth of information regarding efficacy and potential adverse on-target effects in humans.</p>},
  author       = {Orho-Melander, Marju and Gloyn, Anna L.},
  isbn         = {9783319015743},
  language     = {eng},
  month        = {01},
  pages        = {317--336},
  publisher    = {ARRAY(0x94aaf68)},
  series       = {The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation},
  title        = {GCKR : How genetic variation across the allelic spectrum influences protein function and metabolic traits in humans},
  url          = {http://dx.doi.org/10.1007/978-3-319-01574-3_15},
  year         = {2016},
}