Candidate gene studies in pedigrees with maturity-onset diabetes of the young not linked with glucokinase

• Published in: Diabetologia Vol. 38; no. 9; pp. 1055 - 1060
• Main Authors: ZHANG, Y, WARREN-PERRY, M, SAKER, P. J, HATTERSLEY, A. T, MACKIE, A. D. R, BAIRD, J. D, GREENWOOD, R. H, STOFFEL, M, BELL, G. I, TURNER, R. C
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-09-1995
• Subjects: Adolescent; Adult; Age Factors; Age of Onset; Aged; Base Sequence; Biological and medical sciences; Child; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA - blood; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Follow-Up Studies; Genes, Dominant; Genetic Linkage; Genetic Markers; Glucokinase - genetics; Humans; Incidence; Lod Score; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; Pedigree; Phenotype; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone - genetics; Endocrinopathy; Human; Maturity onset diabetes young; Linkage; Enzyme; Family study; Transferases; Adenosine deaminase; Hexokinase; Glucagon like peptide 1; Pedigree; Glucokinase; Hydrolases; Pituitary adenylate cyclase activating peptide
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/BF00402175

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterised by an early age of onset and an autosomal dominant mode of inheritance. Only a proportion of cases are due to mutations in the glucokinase gene. We have studied five Caucasian MODY families, including the first MODY family to be described, with five candidate genes implicated in regulation of insulin secretion. The affected subjects showed more marked hyperglycaemia than that found in subjects with glucokinase mutations. We assessed polymorphic markers close to the genes for glucokinase, hexokinase II, adenosine deaminase, pituitary adenylate cyclase-activating polypeptide receptor, and glucagon-like peptide-1 receptor. Linkage analysis with diabetes gave cumulative log of the odds (LOD) scores of less than -3, implying that mutations in these genes are unlikely to provide a major genetic contribution to this form of MODY.