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Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents

Santoro, Nicola; Zhang, Clarence K.; Zhao, Hongyu; Pakstis, Andrew J.; Kim, Grace; Kursawe, Romy; Dykas, Daniel J.; Bale, Allen E.; Giannini, Cosimo and Pierpont, Bridget, et al. (2012) In Hepatology 55(3). p.781-789
Abstract
Recently, the single nucleotide polymorphism (SNP) identified as rs1260326, in the glucokinase regulatory protein (GCKR), was associated with hypertriglyceridemia in adults. Because accumulation of triglycerides in hepatocytes represents the hallmark of steatosis, we aimed to investigate whether this variant might be associated with fatty liver (hepatic fat content, HFF%). Moreover, because recently rs738409 in the PNPLA3 and rs2854116 in the APOC3 were associated with fatty liver, we explored how the GCKR SNP and these two variants jointly influence hepatosteatosis. We studied 455 obese children and adolescents (181 Caucasians, 139 African Americans, and 135 Hispanics). All underwent an oral glucose tolerance test and fasting lipoprotein... (More)
Recently, the single nucleotide polymorphism (SNP) identified as rs1260326, in the glucokinase regulatory protein (GCKR), was associated with hypertriglyceridemia in adults. Because accumulation of triglycerides in hepatocytes represents the hallmark of steatosis, we aimed to investigate whether this variant might be associated with fatty liver (hepatic fat content, HFF%). Moreover, because recently rs738409 in the PNPLA3 and rs2854116 in the APOC3 were associated with fatty liver, we explored how the GCKR SNP and these two variants jointly influence hepatosteatosis. We studied 455 obese children and adolescents (181 Caucasians, 139 African Americans, and 135 Hispanics). All underwent an oral glucose tolerance test and fasting lipoprotein subclasses measurement by proton nuclear magnetic resonance. A subset of 142 children underwent a fast gradient magnetic resonance imaging to measure the HFF%. The rs1260326 was associated with elevated triglycerides (Caucasians P = 0.00014; African Americans P = 0.00417), large very low-density lipoprotein (VLDL) (Caucasians P = 0.001; African Americans, P = 0.03), and with fatty liver (Caucasians P = 0.034; African Americans P = 0.00002; and Hispanics P = 0.016). The PNPLA3, but not the APOC3 rs2854116 SNP, was associated with fatty liver but not with triglyceride levels. There was a joint effect between the PNPLA3 and GCKR SNPs, explaining 32% of HFF% variance in Caucasians (P = 0.00161), 39.0% in African Americans (P = 0.00000496), and 15% in Hispanics (P = 0.00342). Conclusion: The rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels. GCKR and PNPLA3 act together to convey susceptibility to fatty liver in obese youths. (Hepatology 2012) (Less)
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Contribution to journal
publication status
published
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Hepatology
volume
55
issue
3
pages
781 - 789
publisher
John Wiley & Sons
external identifiers
  • wos:000300699900015
  • scopus:84857398069
ISSN
1527-3350
DOI
10.1002/hep.24806
language
English
LU publication?
yes
id
73f7ef13-523f-4f61-a37e-9771462eb310 (old id 2591455)
date added to LUP
2012-06-01 09:37:49
date last changed
2017-07-30 03:58:58
@article{73f7ef13-523f-4f61-a37e-9771462eb310,
  abstract     = {Recently, the single nucleotide polymorphism (SNP) identified as rs1260326, in the glucokinase regulatory protein (GCKR), was associated with hypertriglyceridemia in adults. Because accumulation of triglycerides in hepatocytes represents the hallmark of steatosis, we aimed to investigate whether this variant might be associated with fatty liver (hepatic fat content, HFF%). Moreover, because recently rs738409 in the PNPLA3 and rs2854116 in the APOC3 were associated with fatty liver, we explored how the GCKR SNP and these two variants jointly influence hepatosteatosis. We studied 455 obese children and adolescents (181 Caucasians, 139 African Americans, and 135 Hispanics). All underwent an oral glucose tolerance test and fasting lipoprotein subclasses measurement by proton nuclear magnetic resonance. A subset of 142 children underwent a fast gradient magnetic resonance imaging to measure the HFF%. The rs1260326 was associated with elevated triglycerides (Caucasians P = 0.00014; African Americans P = 0.00417), large very low-density lipoprotein (VLDL) (Caucasians P = 0.001; African Americans, P = 0.03), and with fatty liver (Caucasians P = 0.034; African Americans P = 0.00002; and Hispanics P = 0.016). The PNPLA3, but not the APOC3 rs2854116 SNP, was associated with fatty liver but not with triglyceride levels. There was a joint effect between the PNPLA3 and GCKR SNPs, explaining 32% of HFF% variance in Caucasians (P = 0.00161), 39.0% in African Americans (P = 0.00000496), and 15% in Hispanics (P = 0.00342). Conclusion: The rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels. GCKR and PNPLA3 act together to convey susceptibility to fatty liver in obese youths. (Hepatology 2012)},
  author       = {Santoro, Nicola and Zhang, Clarence K. and Zhao, Hongyu and Pakstis, Andrew J. and Kim, Grace and Kursawe, Romy and Dykas, Daniel J. and Bale, Allen E. and Giannini, Cosimo and Pierpont, Bridget and Shaw, Melissa M. and Groop, Leif and Caprio, Sonia},
  issn         = {1527-3350},
  language     = {eng},
  number       = {3},
  pages        = {781--789},
  publisher    = {John Wiley & Sons},
  series       = {Hepatology},
  title        = {Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents},
  url          = {http://dx.doi.org/10.1002/hep.24806},
  volume       = {55},
  year         = {2012},
}