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

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    Abstrakt

    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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