الفهرس 
CORONARY ARTERY DISEASEOnly 14 pages are availabe for public view
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Abstract
Coronary artery disease, including myocardial infarction, angina pectoris, and stenosis of the coronary arteries, is one of the leading causes of mortality and morbidity worldwide.
Coronary artery disease is a complex multifactorialdisease that is thought to result from aninteraction between the individual’s genetic background andvarious environmental factorssuch as diet, smoking, and physical activity. It is usually associated with conventional risk factors, including hypertension, diabetes mellitus, and dyslipidemia. While there are many traditional and novel risk markers associated with CAD, yet a large gap for CAD risk prediction remains. Epidemiological evidence points to an approximate 50% genetic susceptibility to the disease.
Many different genetic associations with CAD have been identified through family and population based analyses, and genetic risk markers may be important for better defining individuals at risk for cardiovascular events. One of these most famous genes is the lipoprotein lipase (LPL) gene encoding for the lipoprotein lipase enzyme.
Lipoprotein Lipase enzyme plays a central role in lipoprotein metabolism by hydrolyzing triglyceride- rich particles in muscle, adipose tissue, and macrophages. LPL plays a non catalytic bridging role as a ligand in lipoprotein- cell surface interactions and receptor-mediated uptake of lipoproteins with its ability to bind simultaneously to both lipoproteins and cell surface receptors which mediates the cellular uptake of lipoproteins.
The LPL gene is located on chromosome 8p22, with 9 exons and 29.6 kb. More than 100 mutations have been identified in the LPL gene. Many of them have been associated with markedly reduced enzyme activity, whereas several relatively common variants have been associated with moderate changes in LPL catalytic function. The highly polymorphic LPL gene and its many single nucleotide polymorphisms in both the coding region and the non coding region have been studied for their associations with lipids, lipoproteins, and atherosclerosis.
Several restriction fragment length polymorphisms in the LPL gene have been documented and associated with various lipid traits. The HindIII polymorphism is a base transition of thymine (T) to guanine (G) at position +495 in intron 8 which, abolishes the restriction site for the enzyme HindIII. The S447X polymorphism is characterized by the substitution of cytosine (C) by guanine (G) at position 1595 in exon 9, resulting in a premature stop codon, which removes the last two amino acids of the protein
In the present study, the aim of the work was to study the impact of the genetic variants of lipoprotein lipase (S447X and HindIII) on lipid metabolism and angiographic severity of coronary artery disease. The severity of CAD was determined from the number of significant (50%) stenosis of the major coronary arteries.
In the present study 60 venous samples were collected from CAD patients, in addition to 50 venous samples from healthy controls. These samples were tested for lipid profile (total cholesterol, TG, HDL-C and LDL-c) and Lipoprotein lipase gene polymorphisms (HindIII and S447X) by PCR_ RFLP technique.
There were 16 CAD patients who had H+H+ genotype, 33 had H+H- genotype, while 11 CAD patients had H-H- genotype. Concerning the S447X polymorphism, 50 CAD patients had the SS genotype, 10 patients had SX genotype, while none of the patients had the XX genotype.
The frequency of X allele was significantly higher in the control group compared to the CAD patients showing a possible negative significant frequency of the presence of X allele and the development of CAD. However, no significant statistical difference was found between the two groups as regards HindIII alleles (H+ and H-).
As regards the influence of HindIII and S447X on lipid blood levels, considering the HindIII polymorphism, the data of the present study revealed a significant difference in TG/HDL-C ratio being higher in H+ allele carriers when compared with the H- allele carriers. Data of the present study also revealed that the X allele was associated with highly significant lower TG/HDL-C ratio (risk ratio III) in the control group as compared to the CAD patients.
The H- X haplotypes were associated with highly significant lower triglycerides levels and highly significant lower triglyceride/ HDL-c ratio when compared to H+S haplotype.
In conclusion, the results of the present study showed that carriers of the X allele had a better TG/ HDL-c ratio and that H-X haplotype carriers had lower TG levels and a better TG/ HDL-c ratio. Therefore, H-X can be considered one of the protective factors against development of CAD and the knowledge of LPL polymorphisms can be considered a path to a better understanding of genetic influence on TG metabolism and CAD risk.