Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus

NON-INSULIN-DEPENDENT diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown 1,2 . Genetic linkage has been investigated in multigeneration families to localize,...

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Published in:Nature (London) 1992-03, Vol.356 (6365), p.162-164
Main Authors: Froguel, Ph, Vaxillaire, M, Sun, F, Velho, G, Zouali, H, Butel, M. O, Lesage, S, Vionnet, N, Clément, K, Fougerousse, F, Tanizawa, Y, Weissenbach, J, Beckmann, J. S, Lathrop, G. M, Passa, Ph, Permutt, M. A, Cohen, D
Format: Article
Language:English
Subjects:
Adenosine Deaminase - genetics
Base Sequence
Biological and medical sciences
Blood Glucose - metabolism
chromosome 7
Chromosomes, Human, Pair 7
Diabetes
diabetes mellitus
Diabetes Mellitus, Type 2 - enzymology
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
DNA - chemistry
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
genes
Genetic factors
Genetic Linkage
Genetics
Glucokinase - genetics
Heterogeneity
Human genetics
Humanities and Social Sciences
Humans
Insulin
letter
Life Sciences
Lod Score
Medical research
Medical sciences
Metabolism
Molecular Sequence Data
Monosaccharide Transport Proteins - genetics
multidisciplinary
Mutation
Pedigree
Polymerase Chain Reaction
Science
Science (multidisciplinary)
World population
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Summary:NON-INSULIN-DEPENDENT diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown 1,2 . Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset 3 . Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis4, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM.
ISSN:0028-0836
1476-4687
DOI:10.1038/356162a0