الفهرس 
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Abstract
SUMMARY AND CONCLUSION
T
ype 1 diabetes mellitus is a common chronic endocrinal disorder affecting children and adolescents. It is a heterogeneous multifactorial disease, however, over the past years, genetic predisposition was found to play a major role in disease susceptibility. Type 1 diabetes mellitus is associated with high morbidity and mortality rates due to its acute and chronic complications. Diabetic nephropathy is a very common chronic microvascular complication and is a leading cause of end stage renal disease and death. Therefore, early prediction and detection of type 1 diabetes mellitus and its complications are crucial.
The low density lipoprotein receptor related protein-5 (LRP5) is an essential co-receptor of the Wnt/β catenin signaling pathway. The LRP5 is highly expressed in pancreatic β cells where it is involved in the regulation of pancreatic β cell functions and glucose homeostasis. Many studies on animal models found that LRP5 has a role in insulin signaling and that loss of function of LRP5 leads to glucose intolerance. The LRP5 is highly expressed in kidney tissues as well, however, its role in the kidney is still unclear. Mutations of LRP5 have been associated with many metabolic disorders including diabetes mellitus and kidney disorders.
On the light of the previous data, the aim of the present study was to investigate low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism in type 1 diabetes mellitus and its association with the development of diabetic nephropathy.
This study was conducted on 40 T1DM pediatric and adolescent patients and 20 healthy, age and sex matched children and adolescents as a control group. Patients’ group was subdivided into two subgroups; subgroup Ia included 20 patients without DN and subgroup Ib included 20 patients with DN. All participants were subjected to full history taking, clinical examination including blood pressure measurement, calculation of body mass index, assay of fasting blood glucose, glycated hemoglobin (HbA1c) %, lipid profile, serum creatinine level, calculation of estimated glomerular filtration rate (eGFR), assessment of micro-albumin to creatinine ratio and determination of LRP5 rs3736228 gene polymorphism by real time polymerase chain reaction.
Genotyping of the LRP5 C/T (rs3736228) polymorphism in the studied groups revealed the presence of two genotypic variants; CC and CT. The distribution of these genotypes showed a non-statistically significant deviation from Hardy-Weinberg equilibrium.
The current study showed the absence of a statistically significant difference between type 1 diabetes mellitus patients and healthy controls as regards LRP5 rs3736228 genotypes (CC and CT). Moreover, no statistically significant difference was detected between type 1 diabetic patients without nephropathy and patients with nephropathy as regards LRP5 rs3736228 gene polymorphism.
Regarding the relation between the clinical and laboratory data of type 1 diabetes mellitus patients and LRP5 rs3736228 gene polymorphism; a statistically significant association was found between the CT genotype of LRP5 rs3736228 gene polymorphism and obesity as well as hypercholesterolemia. On the other hand, no statistically significant association was observed between observed LRP5 genotypes and other clinical or laboratory data.
In conclusion, the present study revealed the absence of a statistically significant association between LRP5 rs3736228 gene polymorphism and type 1 diabetes mellitus as well as the development of diabetic nephropathy. However, the study showed that the CT genotype was significantly associated with obesity and hypercholesterolemia in type 1 diabetic patients.
RECOMMENDATIONS
Performance of further studies with larger sample size and more SNPs of LRP5 to study the role of LRP5 in type 1 diabetes mellitus and diabetic nephropathy.
Conduction of comprehensive studies on the effect of ethnic differences on LRP5 gene polymorphism with respect to type 1 diabetes mellitus.