الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hyperlipidemia is the elevation of lipids including fats, fatty acids, cholesterol, cholesterol esters, phospholipids and triglycerides in the blood stream . There are various complications of hyperlipidemia such as coronary artery diseases (CAD) related to obesity and atherosclerosis . Obesity is increasing at an alarming rate, and its associated disorders are placing a considerable strain on our healthcare systems . Obesity is often accompanied by hyperlipidemia. Both obesity and hyperlipidemia are independently associated with atherosclerosis. In parallel to adults, the prevalence of obesity in children and adolescents has also increased during recent decades . from cross-sectional and longitudinal studies of many countries and different ethnic groups, there is enough evidence that in children and adolescents, obesity is associated with lipid and lipoprotein changes and with other well known risk factors of cardiac disease in adulthood, e.g. insulin resistance and high blood pressure . As the duration of hyperlipidemia is higher, obesity in early life is associated with early stages of atherosclerosis . In childhood obesity, genetic factors should be considered much more than in adult cases; environmental factors are not assumed to be influential as genetic factors . In particular, the genes involved in lipid metabolism, such as those encoding the major apolipoproteins, are thought to be candidate genes for obesity . Apolipoprotein B (Apo B) is a large, amphipathic glycoprotein playing a central role in human lipoprotein metabolism and is coded by ApoB gene located on chromosome 2. One of the two Apo B forms is Apo B-100, which is required for very low-density lipoprotein (VLDL) production in the liver. In addition to being an essential structural component of VLDL, Apo B-100 is also the ligand for LDL-receptor-mediated endocytosis of LDL particles . There are also several known Apo B polymorphisms that were proven to cause hyperlipidemia and cardiovascular disease . One such polymorphism is the EcoRI polymorphism that results in Glu4154Lys amino acid substitution in the 26th exon . In previous studies, a significant direct relationship between EcoRI polymorphism and the serum levels of cholesterol and triglyceride was found. It was thought that these polymorphisms reduce the binding capacity of Apo B to LDL receptors and so cause a decrement in LDL clearance . The aim of this work is to evaluate the role of apolipoprotein B-100 (APOB) EcoRI polymorphism on plasma lipid parameters in obese children and its relation with insulin resistance. This is the first study done in Egypt to determine possible relationships of these parameters. The present study involved 40 obese children (20 males, 20 females), their age ranged between 6 – 12 years. The studied patients were divided according to BMI into 3 groups: Group 1 : included 10 mildly obese patients with class I obesity, BMI; 30 - 34.9 (5 males and 5 females), their ages ranged between 6-12 years. Summary================================================== =159 Group 2 : included 10 moderately obese patients with class II obesity, BMI; 35 - 39.9 (5 males and 5 females), their ages ranged between 6-12 years. Group 3: 20 markedly obese patients with class III obesity; BMI ≥ 40 10 males and 10 females), their ages ranged between 6-12 years. In addition to group 4 : included 20 apparently healthy(BMI= 18.5 - 24.9) age and gender matched subjects as a controls (10 males and 10 females), their ages also ranged between 6- 12 years. For all subjects, the following were done: - History taking and clinical examination. - Anthropometric measurements (weight, height and body mass index to diagnose obesity). - Fasting blood glucose. - Fasting insulin. - HOMA-IR equation was applied to diagnose cases with insulin resistance - Lipid profile. - Lipoprotein electrophoresis. - Determination of Apo-B100 genotypes by PCR- RFLP. The results of this study revealed that: • The studied groups were well matched as regard age and gender. • There was a highly significant statistical difference in the weight and BMI between patients and controls as P value <0.001 . • There was a significant statistical difference in BMI between positive EcoRI polymorphism and negative polymorphisms and so there was a direct positive relationship between ApoB100 ECoRI polymorphism and obesity. • The level of fasting blood glucose , fasting insulin and HOMA-IR for insulin resistance were significantly higher in all patient groups (children with different grades of obesity ) when compared with controls. • The level of total cholesterol, triglycerides, LDL-c and were significantly higher in patients groups (children with different grades of obesity ) when compared with controls. While the level of HDL-c was significantly lower in all patient groups when compared with controls. • The Apo B100 EcoRI polymorphism frequencies were more significantly higher among obese patients than among the controls. So there was a highly significant statistical difference in the ECoRI polymorphism between patients (only one patient had negative polymorphism while 39 representing 97.5 % had positive polymorphism and all the 20 controls representing 100% had negative polymorphism). • Significant association had been confirmed between increased fasting insulin, insulin resistance as evidenced by HOMA- IR equation and positive EcoRI polymorphism. Regarding the relation between serum total cholesterol and ECoRI polymorphism there was a significant statistical difference between positive and negative polymorphism as regard as serum total cholesterol as P value less than 0.05. As regard as the relation between triglycerides and ECoRI polymorphism there was no significant statistical difference between positive and negative polymorphism as regard as serum triglycerides HOMA-IR as P value more than 0.05. As regard as the relation between HDL-c and EcoRI polymorphism there was no significant statistical difference between positive and negative polymorphism as regard as serum HDL-c as P value more than 0.05 . As regard as the relation between LDL-c and ECoRI polymorphism there was a significant statistical difference between positive and negative polymorphism as serum LDL-c as P value less than 0.05. As a comparison between cases and control groups as regards lipoprotein electrophoresis the above obtained results revealed that 100 % of patients showed increase beta band while all the 20 controls representing 100% showed normal pattern and so there was a highly significant statistical difference in the Lipoprotein electrophoresis patterns between patients and controls as P value <0.001 . Finally ,the obtained data demonstrated that E+/E+ and E+/ E_ carriers had significantly higher BMI, fasting glucose, fasting insulin, HOMA IR, TC, LDL-C, increased beta band in lipoprotein electrophoresis and significantly lower HDL-c concentrations than did E_/E_ carriers. In conclusion, this study found that obese pediatric patients having positive ECoRI polymorphism could have a higher risk of having hyperlipidemia in the future. Accordingly, this is the first study to determine the relationship between hyperlipidemia, insulin resistance , APOB EcoRI polymorphism and childhood obesity. For future research, the study groups are planned to be enlarged to obtain more precise results.