Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1α gene and the relationship to β-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus

Jeannet Lauenborg*, P. Damm, J. Ek, C. Glümer, T. Jørgensen, K. Borch-Johnsen, H. Vestergaard, P. Hornnes, O. Pedersen, T. Hansen

*Corresponding author af dette arbejde

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    Abstrakt

    Aims: In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to β-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1α (HNF-1α) gene has been associated with decreased serum insulin and C-peptide responses during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM. Methods: The Ala/Va198 polymorphism was measured in 376 women of Danish origin with previous GDM, and in 724 age-matched and 310 middle-aged glucose tolerant women using polymerase chain reaction-restriction fragment length polymorphism. Results: The allelic frequency of the Ala/Val98 polymorphism was 0.043 [95 % confidence interval (CI) 0.028, 0.057] in women with previous GDM vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in serum C-peptide and insulin levels, respectively, at 30 min during an OGTT. Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P = 0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels, respectively, compared with 956 Ala/Ala control subjects. Conclusions: The Ala/Val polymorphism at codon98 of HNF-1α is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM.

    OriginalsprogEngelsk
    Sider (fra-til)1310-1315
    Antal sider6
    TidsskriftDiabetic Medicine
    Vol/bind21
    Udgave nummer12
    DOI
    StatusUdgivet - 1 dec. 2004

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