MOLECULAR GENETICS OF GESTATIONAL DIABETES MELLITUS--A GENETIC PREDISPOSITION

发生妊娠期糖尿病（GDM）的妇女在妊娠期外进展为糖尿病的比率>5%/年，因此，相当大比例的非胰岛素依赖型糖尿病（NIDDM）患者在诊断时的平均年龄相对较低。 此外，b细胞功能受损是GDM女性患DM风险的重要早期预测因素。 基于这些原因，我们假设妊娠期糖尿病（GDM）妇女与NIDDM的其他表现相比，具有一组独特的遗传特征。 这些研究旨在建立一个基因组DNA库和几组参与者的表型信息，包括（i）GDM病史后的NIDDM女性，（ii）具有正常葡萄糖耐量的GDM病史的女性，（iii）没有GDM病史的女性，（iv）典型的晚发型NIDDM患者（定义为50岁以后发病），和（v）具有正常葡萄糖耐量但基于NIDDM一级亲属的家族史、年龄超过50岁或种族（非裔美国人、西班牙裔或美洲土著人）处于晚发NIDDM风险因素的个体的参照组。这些DNA和表型信息将用于在当前和未来的研究中解决我们的假设，方法是检查先前鉴定的易患年轻人成熟型糖尿病（MODY）、NIDDM、和肥胖（NIDDM的一个危险因素），以及这些多态性与糖尿病的关系。具有不同表型特征改变的突变。 在拟议研究中进行的具体分析将确定与其他四组相比，有GDM病史的NIDDM女性中转录因子肝细胞核因子-1a突变的患病率。 该基因的突变会导致年轻人的成熟型糖尿病（MODY），因此与年轻时糖尿病的发病有关。

Women who develop gestational diabetes mellitus (GDM) progress to diabetes outside of pregnancy at a rate >5%/year and acount, therefore, for a sizable proportion of people with non-insulin dependent diabetes mellitus (NIDDM) whose mean age at diagnosis is relatively young. Moreover, impaired b-cell function is an important early predictor of the risk of developing DM among women with GDM. for these reasons, we have hypothesized that women with gestational diabetes mellitus (GDM) share a unique set of genetic characteristics apart from other presentations of NIDDM. The proposed studies are designed to create a bank of genomic DNA from and phenotypic information on several groups of participants, including (i) women with NIDDM subsequent to a history of GDM, (ii) women with a history of GDM who have normal glucose tolerance, (iii) women who do not have a history of GDM, (iv) individuals with typical, late-onset NIDDM (defined as onset after age 50), and (v) a reference group of individuals with normal glucose tolerance but who are at risk factor for late-onset NIDDM based upon a family history of a first degree relative with NIDDM, age over 50, or ethnicity (African-American, Hispanic, or Native American). This DNA and phenotypic information will be used to address our hypothesis in the present and future studies by examining the frequency of polymorphisms/mutations in previously identified genes that predispose to the development of maturity onset diabetes of the young (MODY), NIDDM, and obesity (a risk factor for NIDDM) in different groups of participants and the association of those polymorphisms/mutations with alterations in the different phenotypic characteristics. The specific analysis that will be conducted in the proposed study will be to determine the prevalence rate of mutations in the transcription factor hepatocyte nuclear factor-1a in women with NIDDM subsequent to a history of GDM compared to the other four groups. Mutations in this gene result in maturity-onset diabetes of the young (MODY) and are, thus, associated with onset of diabetes at a young age.