GLUCOKINASE GENE ISLET PROMOTER REGION VARIANT (G-]A) AT NUCLEOTIDE -30 IS NOT ASSOCIATED WITH REDUCED INSULIN-SECRETION IN FINNS

OBJECTIVE-To investigate the effect of the islet promoter region varia nt (G --> A) at nucleotide -30 of the glucokinase (GCK) gene on insuli n levels in subjects with normal glucose tolerance (NGT), impaired glu cose tolerance (IGT), and NIDDM. RESEARCH DESIGN AND METHODS-The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were perf ormed in all subjects, and intravenous glucose tolerance tests (IVGTTs ) were performed in subjects with NGT. The islet promoter region of th e GCK gene was amplified with polymerase chain reaction and screened f or the variant (-30) using single-strand conformation polymorphism ana lysis. RESULTS-The islet promoter variant (-30) of the GCK gene was fo und in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h ins ulin levels, measured by OGTT, did not differ between subjects with an d without this variant in any of the three groups. Furthermore, first- phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant ( -30) of the GCK gene. CONCLUSIONS-These results indicate that the vari ant (-30) of the islet promoter region of the GCK gene does not have a significant effect on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.