الفهرس 
PREMATURE CORONARY ARTERY DISEASE
Novel and Emerging Risk FactorsOnly 14 pages are availabe for public view
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Abstract
Premature coronary artery disease (PCAD) is defined as CAD which manifests for the first time under the age of 55 years for males and under 65 years for female. Risk factors for CAD are both environmental and genetic. Accumulating evidences have shown close associations of genetic polymorphisms in candidate genes with the risk of CAD, especially the early-onset CAD.
Scavenger receptor class B type1 (SCARB 1) is a multi-ligand cell surface receptor expressed both on macrophages and on liver cells, indicating a major role for clearance of excess cholesterol from the body. This membrane protein facilitates the uptake of cholesterol esters from high-density lipoprotein cholesterol (HDL-C) and drives cholesterol from tissues to the liver in the various stages of reverse cholesterol transport pathway.
SCARB 1 is encoded by the SCARB 1 gene (human gene ID 949) located on chromosome 12q24.31. Several genetic studies in various populations have discovered multiple SCARB 1 variants and reported their relationship with lipid traits, subclinical atherosclerosis and incidence of coronary artery disease.
Several studies on rs5888 polymorphism and the risk of CAD have been previously published with contradictory results. There is even controversy about which allele confers increased risk.
In this regards, the objective of our study was to investigate the association of rs5888 polymorphism of SCARB 1 gene and premature coronary artery disease and to assess its relationship with the severity of the disease.
This study was conducted on fifty (50) patients with premature coronary artery disease who were recruited from cardiology Department of Ain Shams University Hospitals in addition to fifty (50) age and sex matched non coronary artery disease controls. All individuals included in this study were subjected to full history taking focusing on risk factors of coronary artery disease including: Family history of premature coronary disease, hypertension and smoking. Thorough clinical examination including general and local examination. Coronary angiography and Laboratory investigations including: Full lipid profile (total cholesterol, triglycerides, HDL-C and LDL-C) and Detection of rs5888 polymorphism of SCARB 1 gene by real-time polymerase chain reaction (PCR) and high resolution melting analysis (HRM). The severity of PCAD was assessed using Gensini score for patients only.
The study revealed that
The frequency of the wild type (CC) was higher in the non- PCAD group (56%) than patients’ group (18%) and it can be considered as a negative risk factor for PCAD for all patients even when they were stratified by sex.
The homozygous and heterozygous mutations (TT & CT) were statistically more frequently distributed in PCAD patients compared to control subjects and the CT genotype was considered as positive risk factor for PCAD in all patients and in male subgroup but not in females.
A higher frequency of distribution of T allele was found in patients’ group when compared with control group and it confers a positive risk to PCAD and on the other hand, the higher frequency of distribution of C allele was found in control non- PCAD group when compared to patients’ group conferring a negative risk for PCAD.
The studied SNP correlated with severity of PCAD using Gensini score, for the score being higher in homozygous and heterozygous mutant forms.
In Conclusion
Our study has shown that the wild (CC) genotype and the C allele confer a negative risk for PCAD. On the other hand, the mutant (CT and TT) genotypes together with the T allele of SCARB 1 SNP rs5888 were associated with increased risk of PCAD in both male and females.
Moreover, a significant association between SCARB 1 SNP rs5888 and disease severity calculated by Gensini score.