对有或无既往妊娠糖尿病的糖耐量正常女性在口服葡萄糖耐量试验期间肝细胞细胞核因子-1α基因的丙氨酸/缬氨酸98多态性及其与β细胞功能关系的研究。

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.

作者信息

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

机构信息

Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.

出版信息

Diabet Med. 2004 Dec;21(12):1310-5. doi: 10.1111/j.1464-5491.2004.01343.x.

DOI:10.1111/j.1464-5491.2004.01343.x

PMID:15569134

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.

摘要

目的

在妊娠期糖尿病（GDM）合并妊娠中，由于β细胞功能障碍，胰岛素需求增加但未得到满足。肝细胞细胞核因子-1α（HNF-1α）基因第98位密码子的丙氨酸/缬氨酸（Ala/Val）多态性与糖耐量正常受试者口服葡萄糖耐量试验（OGTT）期间血清胰岛素和C肽反应降低有关。本研究的目的是评估该多态性对有或无既往GDM的糖耐量正常女性OGTT血清胰岛素和C肽反应的影响，并调查该多态性是否与GDM相关。

方法

采用聚合酶链反应-限制性片段长度多态性方法，对376名有既往GDM的丹麦女性、724名年龄匹配的糖耐量正常女性和310名中年糖耐量正常女性进行Ala/Val98多态性检测。

结果

有既往GDM的女性中，Ala/Val98多态性的等位基因频率为0.043[95%置信区间（CI）0.028，0.057]，年龄匹配女性中为0.037（95%CI 0.028，0.047），中年女性中为0.039（95%CI 0.024，0.054）。在117名有既往GDM的糖耐量正常女性中，10名Ala/Val98多态性携带者在OGTT期间30分钟时血清C肽和胰岛素水平分别无显著降低27%和22%。与956名Ala/Ala对照受试者相比，78名携带Ala/Val98多态性的对照受试者血清C肽和胰岛素水平分别降低10%（P = 0.001）和16%（P = 0.004）。