Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene and the relationship to beta-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus.
OBJECTIVE
In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha) 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/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 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-1alpha 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.
Lauenborg
J
J
Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. jeannet@lauenb.org
Damm
P
P
Ek
J
J
Glümer
C
C
Jørgensen
T
T
Borch-Johnsen
K
K
Vestergaard
H
H
Hornnes
P
P
Pedersen
O
O
Hansen
T
T
D000328:Adult; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics*
D002096:C-Peptide; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007328:Insulin; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1