Department of Epidemiology, Faculty of Medicine, University of Ulm, Albert-Einstein-Allee 47, D-89081 Ulm, Germany.
Eur J Endocrinol. 2011 Apr;164(4):513-20. doi: 10.1530/EJE-10-0842. Epub 2011 Jan 11.
To determine prevalence, genetic and phenotype characteristics of patients with hepatocyte nuclear factor-1α (HNF1A) variants in the Diabetes Patienten Verlaufsdokumenation (DPV) multicentre database and to examine the influence of HNF1A mutation type, or location on clinical phenotypes.
Seventy-one DPV patients were labelled as HNF1A-MODY (MODY3). Forty-four patients carried HNF1A mutations, while 27 patients were found to have HNF1A polymorphisms only. Associations between mutation type/position and age at disease onset, HbAlc, body mass index (BMI), diagnosis, family history and treatment modality were analysed using non-parametric statistics (Wilcoxon test).
Patients with HNF1A mutations were 36% male, aged 14.1±5.8 years at diagnosis, and slightly overweight (BMI-SDS: +0.8±1.1). Treatment was lifestyle intervention (20.5%), insulin (35.3%), oral anti-diabetic (OAD, 43%) and both insulin+OAD (15.9%). More patients with missense mutations (60%) than patients with nonsense mutations/frameshift (23.8%) did not use insulin (P=0.03). No differences were found with regard to mutation types, isoform or domain. We identified several previously undescribed mutations in the cohort including c.-158insGGGTTGG in the promoter region, G31X, E41X, Q130X, L162P, R245I, A269P, S355X, Q398X, Q473X, Q495X, E508X, P588fs-insGCCA and P588fs-delAC. Patients carrying HNF1A polymorphisms were significantly younger at diagnosis than patients with HNF1A mutations (10.9±4.2 vs 14.19±5.8 years; P=0.027), and all carried I27L, S487N and A98V (n=3).
HNF1A-MODY is the second most frequent MODY diagnosis registered in the DPV database, and previously undescribed HNF1A mutations account for about one-third of HNF1A-MODY cases. Patients with HNF1A polymorphisms documented as HNF1A-MODY were misclassified. They may have autoantibody-negative type 1B or type 2 diabetes or may have other MODY types.
在糖尿病患者病程文档（DPV）多中心数据库中确定载有肝细胞核因子-1α（HNF1A）变异的患者的患病率、遗传和表型特征，并研究 HNF1A 突变类型或位置对临床表型的影响。
71 名 DPV 患者被标记为 HNF1A-MODY（MODY3）。44 名患者携带 HNF1A 突变，而 27 名患者仅携带 HNF1A 多态性。使用非参数统计（Wilcoxon 检验）分析突变类型/位置与发病年龄、HbAlc、体重指数（BMI）、诊断、家族史和治疗方式之间的关系。
HNF1A 突变患者中男性占 36%，诊断时年龄为 14.1±5.8 岁，体重稍超重（BMI-SDS：+0.8±1.1）。治疗方法为生活方式干预（20.5%）、胰岛素（35.3%）、口服降糖药（OAD，43%）和胰岛素+OAD（15.9%）。与无意义突变/移码突变（23.8%）相比，具有错义突变的患者（60%）更不使用胰岛素（P=0.03）。在突变类型、同工型或结构域方面未发现差异。我们在队列中发现了一些以前未描述的突变，包括启动子区域的 c.-158insGGGTTGG、G31X、E41X、Q130X、L162P、R245I、A269P、S355X、Q398X、Q473X、Q495X、E508X、P588fs-insGCCA 和 P588fs-delAC。携带 HNF1A 多态性的患者诊断时的年龄明显小于携带 HNF1A 突变的患者（10.9±4.2 岁 vs 14.19±5.8 岁；P=0.027），并且所有患者均携带 I27L、S487N 和 A98V（n=3）。
HNF1A-MODY 是 DPV 数据库中登记的第二常见 MODY 诊断，以前未描述的 HNF1A 突变约占 HNF1A-MODY 病例的三分之一。被标记为 HNF1A-MODY 的 HNF1A 多态性患者被错误分类。他们可能患有自身抗体阴性 1 型或 2 型糖尿病，或者可能患有其他 MODY 类型。
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