The impact of genetic variation in the G6PC2 gene on insulin secretion depends on glycemia.
J Clin Endocrinol Metab
; 95(12): E479-84, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20826583
ABSTRACT
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:
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 OUTCOMEMEASURE:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Glicemia
/
Glucose-6-Fosfatase
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Polimorfismo de Nucleotídeo Único
/
Insulina
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2010
Tipo de documento:
Article