Study of genetic polymorphism in diabetes mellitus

Abstract

Diabetes Mellitus (DM) is an advanced and chronic endocrine disorder characterized by insufficiency of insulin secretion from pancreatic beta cells or of insulin resistance in peripheral tissues such as liver, adipose tissues and skeletal muscles. Glucokinase (ATP: D-glucose-6-phosphotransferase; GCK), initiates glycolysis and acts as a glucose sensor and metabolic signal producer in liver and pancreas. The present study investigated differences in allelic frequencies between 60 individual diabetics with typeII and 60 healthy controls. Clinical manifestations identified, GCK gene was selected analyzed data were compared to RFLP of the glucokinase gene and results confirmed about mutation. There were also significant differences (P<0.0001) in glycation levels (0.90, 0.4838mole/mole), random blood sugar (348.8, 105.8 mg/dl), cholesterol levels (235.3, 161.8 mg/dl), low density lipoprotein in diabetic subjects (155.3, 28.46 mg/dl) and in healthy donors. GCK gene mutations were found in 70% of the patients while 30% are non-mutated. The basic aim of this study is to understand the mechanism and genes which are responsible for the prevalence of diabetes and to investigate new trends and methods used for the treatment of this disease. A hereditary variation of a gene is mentioned in this study, it is a change in a nucleotide sequence with an addition, deletion, or investment of a nucleotide sequence. In particular, genetic variation in a gene includes a single nucleotide polymorphism. Samples show the mutation insertion, deletion and insertion/deletion. PCR-sequencing showed qualitative differences in diabetic patients in comparison to non-diabetics. Glucokinase is the most important component in glucose detection of pancreatic islet beta cells in diabetes because glucokinase mutations can be one of the most common single gene disorders described. It is known that a genetic variation of a human glucokinase gene, including a point mutation, causes MODY, concentration of plasma glucose increased and it is supposed to be the cause of diabetes of the present study subjects. The main aspects of the work were designed to investigate immunological cross-reactivity between viral antigens and pancreas-specific self-antigens. This is to investigate, hypothesis that type1 diabetes may be triggered following infection with commonly occurring viruses such as coxsackie B, rotavirus, rubella, mumps and cytomegalovirus. The ANOVA of peripheral blood CD3+ T cells in healthy controls expresses higher level (1.475 ± 0.2930), than the diabetic patients (0.685±0.0927). CD14+ T-cell on monocyte1 frequency were analysed by flow-cytometry in the same Diabetes Mellitus patients expressing the higher level in healthy control (10.79±9.225) when compared to diabetic subjects (2.615±0.5850) and CD14+ on monocyte2 in healthy subjects’ level is higher (11.41±9.925) as compared to the diabetes (2.415±1.575). B-Cell marker CD19+ in healthy donors show higher significant level (5.085±5.055) and in diabetic subjects it is comparatively lowers (3.615±1.825). In conclusion, this study proved that oxidative stress increases the production of ROS causes the hyperglycaemic control stimulates the failure of different cells like lymphocytes subsets ultimate causes the cell death.