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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
Author(s) -
Lauenborg J.,
Damm P.,
Ek J.,
Glümer C.,
Jørgensen T.,
BorchJohnsen K.,
Vestergaard H.,
Hornnes P.,
Pedersen O.,
Hansen T.
Publication year - 2004
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2004.01343.x
Subject(s) - medicine , gestational diabetes , endocrinology , insulin , c peptide , diabetes mellitus , glucose tolerance test , polymorphism (computer science) , allele , gestation , insulin resistance , pregnancy , gene , biology , genetics
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/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‐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.