Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.
Mol Cell Biochem. 2010 Dec;345(1-2):223-9. doi: 10.1007/s11010-010-0576-5. Epub 2010 Aug 22.
Involvement of mitochondrial and nuclear gene mutations in the development of type 2 diabetes (T2D) has been established well in various populations around the world. Previously, we have found the mitochondrial A>G transition at nucleotide position 3243 and 8296 in the T2D patients of Coimbatore population. This study is aimed to screen for the presence of various mitochondrial and nuclear DNA mutations in the T2D patients of Coimbatore to identify most prevalent mutation. This helps in identifying the susceptible individuals based on their clinical phenotype in future. Blood samples were collected from 150 unrelated late-onset T2D patients and 100 age-matched unrelated control samples according to World Health Organization criteria. Genotyping for the selected genes was done by polymerase chain reaction-single strand confirmation polymorphism, direct sequencing, and polymerase chain reaction-restriction fragment length polymorphism. The mitochondrial T>C transition at 8356 and nuclear-encoded GLUT1 gene mutation were found in the selected T2D patients. The T8356C mutation was found in two patients (1.3%), and the clinical characteristics were found to be similar in both the patients whereas GLUT1 gene mutation was found in seven patients. Four out of seven patients showed homozygous (-) genotype and three patients showed heterozygous (±) genotype for the mutant allele XbaI. Among these three patients, one patient was found to have elevated level of urea and creatinine with the history of kidney dysfunction and chronic T2D. Our results suggest that the T8356C and GLUT1 gene mutations may have an important role in developing late-onset T2D in Coimbatore population. Particularly, individuals with GLUT1 gene may develop kidney dysfunction at their later age.
线粒体和核基因突变与 2 型糖尿病(T2D)的发生发展有关,这在全球不同人群中已得到很好的证实。此前,我们已经在 Coimbatore 人群的 T2D 患者中发现了线粒体核苷酸位置 3243 和 8296 的 A>G 转换。本研究旨在筛选 Coimbatore T2D 患者中是否存在各种线粒体和核 DNA 突变,以确定最常见的突变。这有助于根据他们未来的临床表型确定易感个体。根据世界卫生组织的标准,从 150 名无血缘关系的迟发性 T2D 患者和 100 名年龄匹配的无血缘关系的对照样本中采集血液样本。通过聚合酶链反应-单链确认多态性、直接测序和聚合酶链反应-限制性片段长度多态性对选定基因进行基因分型。在选定的 T2D 患者中发现了线粒体 T>C 转换和核编码 GLUT1 基因突变。T8356C 突变在两名患者(1.3%)中发现,两名患者的临床特征相似,而 GLUT1 基因突变在 7 名患者中发现。这 7 名患者中有 4 名表现为纯合子(-)基因型,3 名表现为杂合子(±)基因型。在这 3 名患者中,有 1 名患者有肾功能障碍和慢性 T2D 的病史,其尿素和肌酐水平升高。我们的结果表明,T8356C 和 GLUT1 基因突变可能在 Coimbatore 人群中迟发性 T2D 的发生发展中起重要作用。特别是,具有 GLUT1 基因突变的个体可能会在晚年出现肾功能障碍。