title: The beta cell glucokinase promoter variant is an unlikely risk factor for diabetes mellitus. Diabetes Incidence Study in Sweden (DISS).
abstract: Glucokinase plays an important role in the regulation of insulin secretion and is therefore an attractive candidate gene for both insulin dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. A single G-A nucleotide polymorphism at the -30 position of the beta-cell specific promoter region of the glucokinase gene was previously associated with reduced beta-cell function. In the present study we analysed 268 consecutive newly diagnosed Swedish patients classified with either IDDM (n = 205), NIDDM (n = 31) or unclassifiable (n = 32) diabetes between the ages of 15 and 35 years along with a group of 158 age- and sex-matched control subjects. The beta-cell promoter region was amplified by the polymerase chain reaction and the G-A variant identified by single strand conformational polymorphism. There was no significant difference in allele frequencies of G and A between any of the subject groups and likewise, no significant difference in the frequencies of the G/G, G/A, or A/A genotypes. Eight subjects were homozygous for the less common A allele, five had IDDM and three were control subjects. Our results suggest that the -30 beta-cell glucokinase promoter variant is not associated with IDDM.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lotfi
authors.forename: G
authors.initials: G
authors.lastname: Sund
authors.forename: R
authors.initials: R
authors.lastname: Lowe
authors.forename: J
authors.initials: J
authors.lastname: Graham
authors.forename: M
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: S
authors.initials: S
authors.lastname: Deeb
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D003920:Diabetes Mellitus / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics*; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry / Q000201:enzymology*; D016015:Logistic Models; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D013548:Sweden
chemical_list: D017931:DNA Primers; D005941:Glucokinase