Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus amongst South Indians

McCarthy, M I and Hitchins, M and Hitman, G A and Cassell, P G and Hawrami, K and Morton, N and Mohan, V and Ramachandran, A and Snehalatha, C and Viswanathan, M (1993) Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus amongst South Indians. Diabetologia, 36 (7). p. 633. ISSN 0012-186X

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Abstract

Summary Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3) and GCK(5)) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5) marker; however, there were significant differences in allele frequencies at the GCK(3) marker between the Type 2 diabetic subjects and control subjects ( 2=11.6, df=3, p=0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z+2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score <–2) at a recombination fraction of zero under five of the ten models used and highly unlikely (–2 < lod score <–1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.

Item Type:Article
Official URL/DOI:http://dx.doi.org/10.1007/BF00404073
Uncontrolled Keywords:Type 2 (non-insulin dependent) diabetes mellitus ; glucokinase ; genetics ; linkage
Subjects:Diabetology > Diabetes Mellitus Type 2
Biochemistry,Cell and Molecular Signalling
Diabetes
Divisions:Department of Epidemiology
Department of Diabetology
Department of Advanced Research Biochemistry
ID Code:307
Deposited By:INVALID USER
Deposited On:21 Dec 2009 10:44
Last Modified:21 Dec 2009 10:44

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