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Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension
Ji, Y.J.; Yiorkas, A.M.; Frau, F.; Mook-Kanamori, D.; Staiger, H.; Thomas, E.L.; ... ; Yaghootkar, H. 2019
Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension
Article / Letter to editor
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Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated insulin secretion and disposition index in women, but not in men
Raalte, D.H. van; Leeuwen, N. van; Simonis-Bik, A.M.; Nijpels, G.; Haeften, T.W. van; Schafer, S.A.; ... ; Hart, L.M. 't 2012
Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated insulin secretion and disposition index in women, but not in men
Article / Letter to editor
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The Impact of Genetic Variation in the G6PC2 Gene on Insulin Secretion Depends on Glycemia
Heni, M.; Ketterer, C.; Hart, L.M. 't; Ranta, F.; Haeften, T.W. van; Eekhoff, E.M.; ... ; Fritsche, A. 2010
The Impact of Genetic Variation in the G6PC2 Gene on Insulin Secretion Depends on Glycemia
Article / Letter to editor
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Context: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are associated with fasting glucose and insulin secretion. These SNPs are not associated with type 2 diabetes risk. Objective:... Show moreContext: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are associated with fasting glucose and insulin secretion. These SNPs are not associated with type 2 diabetes risk. Objective: Our objective was to investigate whether the impact of the SNP on variables of glucose-stimulated insulin secretion is influenced by glucose tolerance status. Design, Setting, Participants, and Intervention: In this cross-sectional study, we genotyped 1505 healthy Caucasian subjects [normal glucose tolerance (NGT), 1098; impaired glucose tolerance (IGT)/impaired fasting glucose(IFG), 407] for SNP rs560887 within the G6PC2 locus. A subgroup of 326 subjects underwent an iv glucose tolerance test, and 512 participants took part in a hyperinsulinemic-euglycemic clamp. For replication, SNP rs560887 was genotyped in 457 subjects(NGT, 265; IGT, 192) from four independent German and Dutch studies who underwent a hyperglycemic clamp. Main Outcome Measure: Insulin secretion was evaluated. Results: Carriers of the major G-allele exhibited increased fasting glycemia (P < 0.0001). Insulin sensitivity and secretion were not associated with the SNP (P >= 0.06). Glucose tolerance status and genotype interacted on insulin secretion (P = 0.036), such that in NGT subjects, the minor A-allele of rs560887 was associated with decreased insulinogenic index (P = 0.044), which was not the case in subjects with IFG/IGT (P = 1.0). During the iv glucose tolerance test, an association of A-allele carriers with decreased first-phase insulin secretion was also observed only in NGT subjects (P = 0.0053). Likewise, in the hyperglycemic clamp group, the A-allele was associated with decreased first-phase insulin secretion only in the NGT group (P = 0.022) but not in the IGT group. Conclusions: The effects of hyperglycemia on insulin secretion override the more subtle effects of genetic variation in the G6PC2 locus on insulin secretion. (J Clin Endocrinol Metab95: E479-E484, 2010) Show less