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Our data indicated that in DMF exposure, GCKR rs780094 may contribute to the risk of liver injury.
the risk alleles showed different metabolic effects: PNPLA3 rs738409-G, the strongest genetic non-alcoholic fatty liver disease (NAFLD) risk factor, did not associate with metabolic changes. Metabolic effects of GCKR rs1260326-T were comparable in many respects to the fatty liver associations
The GCKR rs780094, SLC30A8 rs13266634 and FTO rs9939609 SNPs were demonstrated to be the potential biomarkers for gestational diabetes risk prediction.
The results suggest that the GCKR and G6PC2 genes may contribute to the risk of type 2 diabetes independently and/or in an interactive manner in the Han Chinese population.
Results show that GCKR was associated with hypertriglyceridemia in Mexican Mestizos but not in Mexican Amerindians.
The results of this population-based study provide evidence for a relationship between lipid regulatory gene polymorphisms including GCKR (rs780094), GCKR (rs1260333), FADS (rs174547), and MLXIPL (rs3812316) with dyslipidemia in an Iranian population.
genome-wide association study in US: Data suggest, among white subjects, an SNP in RCN3 (rs34459162) and a missense mutation in GCKR (rs1260236) are associated with serum levels of glycated albumin; among black subjects, an intergenic SNP in PRKCA (rs2438321) is associated with fructosamine levels and an intronic variant in PRKCA (rs59443763) is associated with glycated albumin levels. (RCN3 = reticulocalbin-3)
Interaction of any alcohol exposure with GCKR (rs780094) and A1CF (rs10821905) influenced the risk of gout in Europeans
GCKR rs780094-C is associated with increased risk of gestational diabetes mellitus.[meta-analysis]
Mutations in the genes glucokinase regulatory protein (GCKR), RNase L (RNASEL), leukocyte immunoglobulin-like receptor 3 (LILRA3), and dynein axonemal heavy chain 10 (DNAH10) segregated with elevated HDLc levels in families, while no mutations associated with low HDLc.
rs1260326 T-allele was associated with plasma lactate in European-Americans and African-Americans.
Patients with moderately controlled type 2 diabetes carrying two T alleles displayed higher plasma triglycerides levels than homozygous carriers of the C allele, whereas no differences were observed in healthy individuals.
Three loci showed robust, replicating association with circulating FXI levels: KNG1 (rs710446, P-value = 2.07 x 10-302), F11 (rs4253417, P-value = 2.86 x 10-193), and a novel association in GCKR (rs780094, P-value = 3.56 x10-09), here for the first time implicated in FXI regulation. The two first SNPs (rs710446 and rs4253417) also associated with partial thromboplastin time
GCKR association with adiposity and the risk of the nonalcoholic fatty liver disease
The existence of a liver-specific FOXA2-regulated transcriptional enhancer at an intronic T2D locus represented by rs780094, rs780095, and rs780096 SNPs that increases GCKR expression is demonstrated.
GCKR Leu446 may influence FGF21 expression via its ability to increase glucokinase (GCK) activity. This can lead to enhanced FGF21 expression via elevated fatty acid synthesis, consequent to the inhibition of carnitine/palmitoyl-transferase by malonyl-CoA, and via increased glucose-6-phosphate-mediated activation of the carbohydrate response element binding protein, known to regulate FGF21 gene expression.
Data suggest that hepatic glucokinase activity is regulated by reversible binding to specific inhibitor protein glucokinase regulatory protein (GKRP) and by binding to activator proteins such as 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK2/FBP2); changes in glucokinase expression and activity are associated with poorly controlled type 2 diabetes and nonalcoholic fatty liver disease. [REVIEW]
The rs780094 [1.34 (1.21-1.49); p = 8.57 x 10(-8) ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 x 10(-6) ] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease.
Carriers of the C allele of rs780094 were 1.41 (odds ratio, 95% CI, 0.97-2.03) times more likely to develop Gestational Diabetes.
Among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults.
This study showed that Sirt2-dependent GKRP deacetylation improves impaired HGU and suggest that it may be a therapeutic target for type 2 diabetes.
Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies.
Glucokinase regulatory protein binds to a super-open conformation of GK mainly through hydrophobic interaction, inhibiting the GK activity by locking a small domain of GK.
This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY).
glucokinase regulatory protein
, glucokinase regulator
, LOW QUALITY PROTEIN: glucokinase regulatory protein
, glucokinase (hexokinase 4) regulator