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

✍ Scribed by Nicola Santoro; Clarence K. Zhang; Hongyu Zhao; Andrew J. Pakstis; Grace Kim; Romy Kursawe; Daniel J. Dykas; Allen E. Bale; Cosimo Giannini; Bridget Pierpont; Melissa M. Shaw; Leif Groop; Sonia Caprio

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 923 KB
• Volume: 55
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.24806

✦ Synopsis

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.