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

J Lauenborg; P Damm; J Ek; C Glümer; T Jørgensen; K Borch-Johnsen; H Vestergaard; P Hornnes; O Pedersen; T Hansen

doi:10.1111/j.1464-5491.2004.01343.x

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

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

15 Citations (Scopus)

Abstract

AIMS: 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.

Original language	English
Journal	Diabetic Medicine
Volume	21
Issue number	12
Pages (from-to)	1310-5
Number of pages	6
ISSN	0742-3071
DOIs	https://doi.org/10.1111/j.1464-5491.2004.01343.x
Publication status	Published - Dec 2004

Keywords

Adult
C-Peptide
Case-Control Studies
DNA-Binding Proteins
Diabetes, Gestational
Female
Glucose Tolerance Test
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Humans
Insulin
Islets of Langerhans
Nuclear Proteins
Polymorphism, Genetic
Pregnancy
Statistics, Nonparametric
Transcription Factors
Journal Article
Research Support, Non-U.S. Gov't

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Lauenborg, J., Damm, P., Ek, J., Glümer, C., Jørgensen, T., Borch-Johnsen, K., Vestergaard, H., Hornnes, P., Pedersen, O., & Hansen, T. (2004). 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. Diabetic Medicine, 21(12), 1310-5. https://doi.org/10.1111/j.1464-5491.2004.01343.x

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. / Lauenborg, J ; Damm, P ; Ek, J et al.
In: Diabetic Medicine, Vol. 21, No. 12, 12.2004, p. 1310-5.

Research output: Contribution to journal › Journal article › Research › peer-review

Lauenborg, J , Damm, P , Ek, J, Glümer, C, Jørgensen, T, Borch-Johnsen, K, Vestergaard, H, Hornnes, P, Pedersen, O & Hansen, T 2004, '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', Diabetic Medicine, vol. 21, no. 12, pp. 1310-5. https://doi.org/10.1111/j.1464-5491.2004.01343.x

Lauenborg J , Damm P , Ek J, Glümer C, Jørgensen T, Borch-Johnsen K et al. 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. Diabetic Medicine. 2004 Dec;21(12):1310-5. doi: 10.1111/j.1464-5491.2004.01343.x

@article{2de21d80ed284cd18536201ae36fd618,

title = "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",

abstract = "AIMS: 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.",

keywords = "Adult, C-Peptide, Case-Control Studies, DNA-Binding Proteins, Diabetes, Gestational, Female, Glucose Tolerance Test, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Humans, Insulin, Islets of Langerhans, Nuclear Proteins, Polymorphism, Genetic, Pregnancy, Statistics, Nonparametric, Transcription Factors, Journal Article, Research Support, Non-U.S. Gov't",

author = "J Lauenborg and P Damm and J Ek and C Gl{\"u}mer and T J{\o}rgensen and K Borch-Johnsen and H Vestergaard and P Hornnes and O Pedersen and T Hansen",

year = "2004",

month = dec,

doi = "10.1111/j.1464-5491.2004.01343.x",

language = "English",

volume = "21",

pages = "1310--5",

journal = "Diabetic Medicine",

issn = "0742-3071",

publisher = "Wiley",

number = "12",

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TY - JOUR

T1 - 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

AU - Lauenborg, J

AU - Damm, P

AU - Ek, J

AU - Glümer, C

AU - Jørgensen, T

AU - Borch-Johnsen, K

AU - Vestergaard, H

AU - Hornnes, P

AU - Pedersen, O

AU - Hansen, T

PY - 2004/12

Y1 - 2004/12

N2 - AIMS: 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.

AB - AIMS: 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.

KW - Adult

KW - C-Peptide

KW - Case-Control Studies

KW - DNA-Binding Proteins

KW - Diabetes, Gestational

KW - Female

KW - Glucose Tolerance Test

KW - Hepatocyte Nuclear Factor 1

KW - Hepatocyte Nuclear Factor 1-alpha

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Nuclear Proteins

KW - Polymorphism, Genetic

KW - Pregnancy

KW - Statistics, Nonparametric

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1464-5491.2004.01343.x

DO - 10.1111/j.1464-5491.2004.01343.x

M3 - Journal article

C2 - 15569134

SN - 0742-3071

VL - 21

SP - 1310

EP - 1315

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 12

ER -