Linkage of type 2 diabetes to the glucokinase gene

Lancet. 1992 May 30;339(8805):1307-10. doi: 10.1016/0140-6736(92)91958-b.


Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes that presents from the second decade and has an autosomal dominant mode of inheritance. We have investigated the glucokinase gene, a candidate gene for diabetes, in two MODY pedigrees. In a large 5-generation pedigree (BX) with 15 diabetic members, use of a microsatellite polymorphism revealed linkage of diabetes to the glucokinase locus on chromosome 7p. A peak lod score of 4.60 was obtained at a recombination fraction (theta) of zero. This finding suggests that a defective glucokinase gene contributes to the diabetes phenotype in this pedigree. This is not universal in MODY since linkage to the glucokinase locus was excluded in a second pedigree M (lod score = -7.36 at theta = 0). The affected members in pedigree BX were diagnosed either when young (in pregnancy or on screening) or when they presented symptomatically in middle and old age; most of them were treated by diet alone. Defects in the glucokinase gene may play an important part in the pathogenesis of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Blood Glucose / analysis
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7*
  • DNA*
  • Diabetes Mellitus, Type 2 / classification
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fasting
  • Female
  • Genes, Dominant / genetics
  • Genetic Linkage / genetics*
  • Genetic Testing
  • Glucokinase / genetics*
  • Glucokinase / physiology
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / genetics
  • Islets of Langerhans / physiopathology
  • Lod Score
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotides / genetics
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Recombination, Genetic


  • Blood Glucose
  • Oligonucleotides
  • DNA
  • Glucokinase