Al-Sheyab Fawzi, Khamaiseh Emran, Halaweh Marwan Abu, Khaul Raida W
Genetic Engineering and Biotechnology Department, Jordan University of Science and Technology, Jordan.
Tsitol Genet. 2009 Sep-Oct;43(5):58-63.
Maturity-Onset Diabetes of the Young(MODY) is a monogenic form of Diabetes Mellitus (DM) characterized by an autosomal dominant inheritance, onset usually before 25 years of age and a primary defect in glucose-stimulated insulin secretion. Glucokinase (GCK) acts as a glucose sensor in the pancreatic beta cell and regulates insulin secretion. The mutation in the gene encoding GCK results in enzyme inactivation cause MODY2. Functional studies of naturally occurring GCK mutations associated with hyperglycaemia provide further insight into the biochemical basis of glucose sensor regulation. In this study 100 diabetic Jordanian patients with MODY2 phenotype and 150 Normal control subjects were screened for the presence of GCK gene mutations including the missense mutations at position Thr228Ala in exon 7, Gly299Arg in exon 8 and nonsense mutation Ser383Ter in exon 9, utilizing polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis. The results shows no Thr228Ala, Gly299Arg and Ser383Ter mutations were detected in both groups, which was differ from the results obtained for Italian and Caucasian from the Oxford region in UK MODY2 patients. Our data indicated that the previously studied mutations in Italian and Caucasian patients in the GCK gene are not common in MODY Jordanian population, suggesting a racial difference can be found in the frequency of the GCK polymorphism.
青年发病的成年型糖尿病（MODY）是糖尿病（DM）的一种单基因形式，其特征为常染色体显性遗传，通常在25岁之前发病，且存在葡萄糖刺激胰岛素分泌的原发性缺陷。葡萄糖激酶（GCK）在胰腺β细胞中充当葡萄糖传感器并调节胰岛素分泌。编码GCK的基因突变导致酶失活，从而引发MODY2。对与高血糖相关的天然存在的GCK突变进行功能研究，可进一步深入了解葡萄糖传感器调节的生化基础。在本研究中，利用聚合酶链反应与限制性片段长度多态性（PCR-RFLP）分析，对100例具有MODY2表型的约旦糖尿病患者和150名正常对照受试者进行筛查，以检测GCK基因突变的存在，包括外显子7中Thr228Ala位置的错义突变、外显子8中Gly299Arg的错义突变以及外显子9中Ser383Ter的无义突变。结果显示，两组均未检测到Thr228Ala、Gly299Arg和Ser383Ter突变，这与英国牛津地区意大利人和白种人MODY2患者的检测结果不同。我们的数据表明，先前在意大利和白种人患者中研究的GCK基因突变在约旦MODY人群中并不常见，这表明在GCK基因多态性频率方面可能存在种族差异。
