Elsevier

The Lancet

Volume 339, Issue 8805, 30 May 1992, Pages 1307-1310
The Lancet

ORIGINAL ARTICLES
Linkage of type 2 diabetes to the glucokinase gene

https://doi.org/10.1016/0140-6736(92)91958-BGet rights and content

Abstract

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 (θ) 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 θ=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.

References (31)

  • A. Matsutani et al.

    A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p

    Genomics

    (1992)
  • Ma Magnuson et al.

    An alternate promoter in the glucokinase gene is active in the pancreatic β-cell

    J Biol Chem

    (1989)
  • Ah Barnett et al.

    Diabetes in identical twins

    Diabetologia

    (1981)
  • B. Newman et al.

    Concordance in type 2 (non-insulin dependent) diabetes mellitus in male twins

    Diabetologia

    (1987)
  • WHO Study Group on Diabetes

    WHO Tech Rep Ser no 727

    (1985)
  • Jte Cook et al.

    NIDDM without affected parents-implications for linkage analysis with genetic markers

    Diabetes

    (1991)
  • S. O'Rahilly et al.

    Type 2 (non-insulin-dependent) diabetes mellitus. New genetics for old nightmares

    Diabetologia

    (1988)
  • Rb Tattersall et al.

    A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people

    Diabetes

    (1975)
  • J. Bell et al.

    Maturity-onset diabetes of the young is not linked to the insulin gene

    Br Med J

    (1983)
  • T. Andreone et al.

    Insulin gene analysis in a family with maturity-onset diabetes of the young

    Diabetes

    (1985)
  • S. O'Rahilly et al.

    Linkage analysis of the human insulin receptor gene in type 2 (non-insulin-dependent) diabetic families and a family with maturity onset diabetes of the young

    Diabetologia

    (1988)
  • Sc Elbin et al.

    Linkage analysis of the human insulin receptor gene and maturity-onset diabetes of the young

    Diabetologia

    (1987)
  • P. Patel, Y-M.D. Lo, A. Hattersley, et al., Linkage analysis of maturity onset diabetes of the young using...
  • S. O'Rahilly et al.

    Analysis of the pro-opiomelancortin gene in non-insulin dependent diabetic families

    Diabetes Res

    (1989)
  • Ra Vinik et al.

    Linkage studies of maturity-onset-diabetes of the young-RW pedigree

    Diabetologia

    (1988)
  • Cited by (347)

    • Glucokinase activity in diabetes: too much of a good thing?

      2023, Trends in Endocrinology and Metabolism
    • Maturity onset diabetes of the young type 2 (MODY2): Insight from an extended family

      2021, Diabetes Research and Clinical Practice
      Citation Excerpt :

      Mutations in GCK (MIM #138079) present with either hyperglycemia or hypoglycemia [13,15,19]. GCK mutations as the cause for MODY2 were first reported in 1992 [20-22], and over 937 different mutations have been described since then (HGMD® Professional 2020.1). Patients with MODY2 have a higher set point for glucose homeostasis and an elevated threshold for glucose-stimulating insulin secretion, presenting with mild asymptomatic stable fasting hyperglycemia (99–150 mg/dL) [10,23-25] and mildly elevated HbA1c within 5.6–7.6% (38–60 mmol/mol) [23].

    View all citing articles on Scopus
    View full text