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- Title
Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1α gene and the relationship toβ-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus.
- Authors
Lauenborg, J.; Damm, P.; Ek, J.; Glümer, C.; Jørgensen, T.; Borch-Johnsen, K.; Vestergaard, H.; Hornnes, P.; Pedersen, O.; Hansen, T.
- Abstract
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 duringan 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/Val98 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 mm 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.
- Subjects
GENETIC polymorphisms; LIVER cells; SERUM; INSULIN; C-peptide; PREGNANCY complications
- Publication
Diabetic Medicine, 2004, Vol 21, Issue 12, p1310
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1111/j.1464-5491.2004.01343.x