الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Type 2 diabetes mellitus is an inheritable metabolic disorder of polygenic nature. Genetic and environmental risk factors play important roles in its development. It is a growing health problem in developed and developing countries. It is the most common form of DM, which accounts for 90% to 95% of all diabetic patients. It is characterized by impaired insulin secretion, peripheral insulin resistance and increased hepatic glucose output leading to hyperglycemia.
TCF7L2 gene belongs to a subfamily of TCF7-like high-mobility group box-containing transcription factors. It encodes a high-mobility box- containing transcription factor involved in the Wnt signaling pathway which is important for lipid and glucose metabolism, pancreatic beta cell proliferation and it is also involved in T2DM.
The rs7903146(C/T) polymorphism in the TCF7L2 gene is one of the most strongly associated polymorphisms with T2DM. It was found that TCF7L2 variant rs7903146 appears to affect risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion due to the effect of TCF7L2 on the sensitivity of the ß-cell to incretins.
The present study aimed to investigate the association of rs7903146(C/T) polymorphism of the TCF7L2 gene with type 2 diabetes mellitus for proper management of the high risk carriers. The study included 42 patients with T2DM as cases and 42 healthy subjects with negative family history of T2DM as controls.
All patients were subjected to history taking and physical examination, estimation of body mass index (BMI), laboratory investigations included estimation of fasting serum glucose , 2 hours post prandial glucose concentration , Lipid profile (total cholesterol, triglyceride, LDL-C & HDL-C) , fasting serum insulin levels ,calculation of HOMA and molecular studies for TCF7L2 gene polymorphism using allele-specific PCR technique.
The results of this study revealed the following:
1. The mean age of the studied patients was 50.31 years old.
2. The mean age of onset of the studied patients was 33.62 years old.
3. The mean blood pressure of the studied patients was 146.9/86.19 mm HG.
4. The mean of fasting blood glucose (FBG),Postprandial Glucose (PPG), total cholesterol level (TCH), triglycerides(TG), low density lipoprotein (LDL)and high density lipoprotein (HDL) were 209.79, 279.48, 221.17, 135.36, 133.12 and 60.71 respectively.
5. HOMA-IR was found to be 6.97
6. Around45% of patients were males while around 54% of patients were females.
7. The frequencies of CC, CT and TT genotypes in the patient group were 16.7%, 61.9% and 21.4 % respectively.
8. The frequencies of CC, CT and TT genotypes in controls were, 11.9 % 57.1% and 31 % respectively.
Summary
54
9. The T allele frequency in patients was 52.4 % while the C allele frequency was 47.6%.
10. The T allele frequency in controls was 59.9% while the C allele frequency was found to be 40.5%.
11. The T allele predominated in both case and control groups.
12. About 17% of patients had high TCH levels, 35 % had high LDL levels and 15% had high TG levels.
13. Positive family history of T2DM was obtained from 11 cases (26.2%).
14. Thirty –five patients (83%) had BMI above 30.
15. Seventeen patients (40%) stated that they were on hypertensive medication.
16. The mean fasting insulin serum level measured in patients was found to be 14.02 uIU\ml while in controls it was found to be 9.43 uIU\ml.
17. Based on statistical testing, the relation between different genotypes in the case group, in the control groups and insulin level was non-signficant indicating that there is no association between genotype and insulin level.
18. The statistical test was significant regarding the association between the age of onset and genotypes in the patient group indicating that the T allele affects the age of onset of in the studied patients.
19. No association was found between rs7903146 polymorphism of the transcription factor 7- like 2 (TCF7L2) gene and the biological parameters measured in the studied patients FBG, PPG, Lipid profile (LDL,HDL,TG and TCH) and HOMA-IR.