Lauenborg J, Damm P, Ek J, Glümer C, Jørgensen T, Borch-Johnsen K, Vestergaard H, Hornnes P, Pedersen O, Hansen T
Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
Diabet Med. 2004 Dec;21(12):1310-5. doi: 10.1111/j.1464-5491.2004.01343.x.
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.
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.
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.
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.
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。
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。
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）。
丹麦女性中，HNF-1α基因第98位密码子的Ala/Val多态性与GDM无关。然而，第98位密码子变体与无既往GDM的糖耐量正常女性OGTT期间血清胰岛素和C肽反应的显著受损有关。
