A variation at position - 30 of the bêta-cell glucokinase gene promoter is associated with reduced bêta-cell function in middle-aged Japanese-American men.
We sought to determine whether a G-A variant at position - 30 of the bêta-cell promoter of the glucokinase (GCK) gene observed to be present more frequently in Japanese-American men with impaired glucose tolerance (IGT) than in Japanese-American men with normal glucose tolerance (NGT) is associated with impaired bêta-cell function.
We studied 125 unrelated Japanese-American men (aged 46-74 years ; mean 61 ± 0.5) who were nondiabetic by a 75-g oral glucose tolerance test (OGTT) (65 had NGT and 60 had IGT).
The presence of the - 30 bêta-cell GCK gene promoter variant was determined by single-strand conformation polymorphism analysis. bêta-cell function was assessed using the ratio of the incremental response in immunoreactive insulin (IRI) to that of glucose during the first 30 min of the OGTT (deltaIRI[30 min-0 min]/deltaglucose[30 min-0 min]) performed at baseline and at 5 years of follow-up. bêta-cell function adjusted for basal IRI ([deltaIRI[30 min-0 min]/deltaglucose[30 min-0 min]]/basal IRI ; the relative insulin response) was also evaluated.
At baseline, the - 30 bêta-cell GCK gene promoter variant was present in 15.4% of subjects with NGT vs. 38.3% of subjects with IGT (P<0.01).
Fasting IRI did not differ between groups.
At baseline, deltaIRI[30 min-0 min]/deltaglucose[30 min-0 min] was significantly lower in subjects with the promoter variant (57 x 10-9 [35 x 10-9 to 95 x 10-9] vs. 77 x 10-9 [55 x 10-9 to 128 x 10-9] ; median [interquartile range] ...
Mots-clés Pascal : Anomalie tolérance glucose, Facteur risque, Cellule B, Glucokinase, Transferases, Enzyme, Gène, Promoteur transcription, Mutation, Déterminisme génétique, Epidémiologie, Homme, Asiatique, Etats Unis, Amérique du Nord, Amérique
Mots-clés Pascal anglais : Impaired glucose tolerance, Risk factor, B-Cell, Glucokinase, Transferases, Enzyme, Gene, Transcription promoter, Mutation, Genetic inheritance, Epidemiology, Human, Asiatic, United States, North America, America
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Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0200105
Code Inist : 002B21E01A. Création : 199608.