title: Functional glucokinase regulator gene variants have inverse effects on triglyceride and glucose levels, and decrease the risk of obesity in children.
abstract: OBJECTIVE
  Recently, the association of the natural variants rs1260326 and rs780094 of the glucokinase regulatory protein (GCKR) gene with increased fasting triglycerides and decreased fasting plasma glucose in diabetic adults was reported; the minor alleles were also found to reduce the risk of type 2 diabetes. The present study examined the possible associations of these variants with triglycerides and glucose levels, their allele distribution and their possible effects on childhood obesity.
  
  
  RESULTS
  A total of 221 obese children and 115 healthy normal-weight children as controls were genotyped using PCR-RFLP methods. Both functional GCKR variants were found in association with elevated serum triglycerides and lower fasting plasma glucose levels. Results of logistic regression revealed that, despite higher triglyceride levels, the carriers of the GCKR variants were more protected against the development of obesity; the adjusted models confirmed the lower risk of obesity for both variants (rs1260326: OR, 0.46; 95% CI, 0.25-0.83; rs780094: OR, 0.41; 95% CI, 0.23-0.74).
  
  
  CONCLUSIONS
  Our findings confirm the inverse modulating effect of functional GCKR variants on triglycerides and glucose levels in obese paediatric patients and healthy normal-weight controls. The results of our study strongly suggest that the minor alleles confer protection against the development of obesity in children. The findings also suggest that the minor alleles of functional GCKR may protect against diabetes and the metabolic syndrome in adults.
authors.affiliation: Department of Medical Genetics and Child Development, University of Pecs, Szigeti út 12, 7624 Pécs, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Horvatovich
authors.forename: S
authors.initials: S
authors.lastname: Bokor
authors.forename: N
authors.initials: N
authors.lastname: Polgar
authors.forename: P
authors.initials: P
authors.lastname: Kisfali
authors.forename: F
authors.initials: F
authors.lastname: Hadarits
authors.forename: L
authors.initials: L
authors.lastname: Jaromi
authors.forename: V
authors.initials: V
authors.lastname: Csongei
authors.forename: J
authors.initials: J
authors.lastname: Repasy
authors.forename: D
authors.initials: D
authors.lastname: Molnar
authors.forename: B
authors.initials: B
authors.lastname: Melegh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D001786:Blood Glucose / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D014280:Triglycerides; D002784:Cholesterol