Large-scale studies of the Hphl insulin gene variable-number-of-tandem- repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

S. K. Hansen*, A. P. Gjesing, S. K. Rasmussen, C. Glümer, S. A. Urhammer, G. Andersen, C. S. Rose, T. Drivsholm, S. K. Torekov, D. P. Jensen, C. T. Ekstrøm, K. Borch-Johnsen, T. Jørgensen, M. I. McCarthy, T. Hansen, O. Pedersen

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstract

    Aims/hypothesis. The class III allele of the variable-number-of-tandem- repeats polymorphism located 5′ of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. Methods. We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes. Results. There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middle-aged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. Conclusions/interpretation. The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

    OriginalsprogEngelsk
    Sider (fra-til)1079-1087
    Antal sider9
    TidsskriftDiabetologia
    Vol/bind47
    Udgave nummer6
    StatusUdgivet - 1 jun. 2004

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