دراسة انزيم التيلومريز وجين الكلوتاثيون بيروكسيديز الاول في مرضى السكري النوع الاول == Telomerase Enzyme And Glutathione Peroxidase1 Gene In Type 1 Diabetes Mellitus Patients
Author name:
دعاء مهدي هادي الحكاك
Supervisor name:
مها فاضل سميسم | علي حسين البياتي
General topic:
Medicine
Specific topic:
Clinical Biochemistry
Degree:
Master
University:
University of Babylon - Faculty Of Medicine - Department Of Biochemistry
Language:
English
University location:
Babylon
First pages:
19T1197 - p.pdf
Abstract:
Type 1 diabetes is characterized by an immune - mediated depletion of ? - cells that results in lifelong dependence on exogenous insulin. Accumulating evidence suggests that oxidative cell injury caused by free radicals contributes to the development of type 1 diabetes mellitus (T1DM) complications and decreased efficiency of antioxidant defenses (both enzymatic and nonenzymatic) seems to correlate with the severity of pathological tissue changes in T1DM, So many studies have tended to analyze the genetic material that can be related to the occurrence of the disease. Different combinations of genetic defects of antioxidant enzyme are expected. This could readily provide an explanation of the heterogeneity of T1DM.The aim of this study is to assess the differences of GPX1 genotype in T1DM as compare with controls. And the effect of C/T at nucleotide 1050450codon 198 of GPX1 gene polymorphisms on serum glutathione peroxidase (GPX) and telomerase enzyme (TE) concentration in T1DM patients and controls. This study included (108) persons, their ages between (28 - 42 years) and body mass index in normal and overweight (68) of them were uncontrolled diabetes type 1 (HbA1c ? 6.5 %), (34) of them were male patients (M group), the other (34) were female patients (F group), and the other (40) apparently healthy as control group (20) male (MC group) with (20) female (FC group). The sera sample of all groups were used to measure the concentration of fasting blood glucose by using colorimetric methods and ELISA method for determination (TE), total antioxidant capacity (TAO - C), glutathione (GSH), and glutathione peroxidase1 enzyme, while whole blood samples from study subjects were used to measure HbA1c and extract DNA for the study of polymorphisms in GPx1 gene.The results of the present study showed1 - A significant increase in glucose, HbA1c in both male and female patients compared with controls group. (P < 0.0001) and (p< 0.05) respectively.2 - The study showed significant decrease (p? 0.001) in telomerase enzyme in both M and F as compare with MC and FC groups,3 - There was no significant association between M and F (P=0.106) and between MC and FC (P=0.327) regarding to gender.4 - The result showed that telomerase concentration significantly decrease with age (p - value<0.001) which indicated by negative correlation between telomerase concentration and age.5 - The result showed significant negative correlation between telomerase enzyme concentration and BMI in patients and controls.6 - The result showed significant decrease in TAO - C in patient as compared with control groups (P=<0.001)7 - GPX1 concentration significantly decreased in patient as compared with control groups (p - value <0.001 )8 - Significant increase in Glutathione concentration in patients as compared with controls (p - value <0.05)9 - Data on the genetic patterns were analyzed using polymerase chain reaction technique - RFLP revealed, were defined as : the codon 198 of Gpx1 genotyping have the homozygous wild - type (CC) Pro/Pro, the homozygous mutant (TT) Leu/Leu, and heterozygous (CT) Pro/Leu allele. There was significant difference between genotype distribution and frequency of alleles between the two groups of patients (M and F) versus (MC and FC) (odds ratio = 33, into confidence level of 95% : 1.65 to 656.26) and P value ( 0.0219) for M vs. MC, and (OR = 12.60, into the proportion of 95% confidence level : 1.93 to 82.08) and P value (0.0081) for F vs. FC. Also, the frequency of TT genotypes in GPX1gene in male and female were47% and 61.7% compare to control male(0%) and female(10%).10 - The allele frequency showed significant differences in all sample (p=0.0013), in male (0.14) and in female (0.0020).11 - There was significant difference in telomerase concentration (p= 0.001) and in glutathione peroxidase concentration (p< 0.0005) in patients group depending on different of the GPX1 genotyping.12 - Depending on GPX1 genotype there were significant differences in BMI in normal weight and in overweight between patient and control (p=0.0375) and (p<0.0018), respectively.In Conclusion, the TT genotype of The GPX1gene variants Pro 198 Leu may be risk factor to T1DM patients. TIDM significantly associated with glutathione peroxidase and telomerase level in patients with TT genotypes of GPX1 gene compared to those with CT and CC genotypes, and this may be considered as a risk factor for senescence and mortality in T1DM. patients, also there is significant negative correlation between telomerase enzyme and BMI in patients and controls.
