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Correlation Between Coronary Artery Disease And The Level Of Serum Lectin-like Oxidized Low-density Lipoprotein Receptor-1 And Its Polymorphism

Posted on:2012-06-22Degree:MasterType:Thesis
Country:ChinaCandidate:J DouFull Text:PDF
GTID:2154330335498864Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
With rising of living standards, improved diet and changing lifestyle,the morbidity of coronary artery disease (CAD) is increasing.CAD is a chronic inflammatory disease, based on atherosclerosis (AS). Oxidized low density lipoprotein (ox-LDL) is an independent risk factor for coronary artery disease and is considered as an initiating factor for atherosclerosis.Recently,researchers discovered lectin-like oxidized low density lipoprotein receptor-1 (LOX-1),a new ox-LDL receptor which may play roles on endothelial injury,promote inflammation,accelerate apoptosis and form foam cell to promote the development of atherosclerosis which then lead to the occurrence of coronary artery disease.Only LOX-1 possesses its unique soluble form among all the scavenger receptors. Serum soluble LOX-1 (sLOX-1) level may reflect the expression of LOX-1 on surface membrane,which can reflect a certain disease state.Therefore,it is likely to play roles on the diagnosis,treatment and prevention of coronary artery disease.Objectives:1. To detect the serum level of sLOX-1 and to evaluate its predictive value on coronary artery disease.2. To investigate the polymorphism of 3'-UTR 188 site of OLR1 gene and to explore the correlation between the gene polymorphism of OLR1 and coronary artery disease.3. To assess the correlation between serum level of sLOX-1 and the polymorphism of 3'-UTR 188 site of OLR1 gene.Methods:1. In this study, we sequentially enrolled 121 patients with coronary artery diseases (CAD), who underwent percutaneous coronary intervention (PCI),75 of them were acute coronary syndrome (ACS) and 46 of them were stable angina pectoris (SAP). Another 50 healthy subjects confirmed by CAG were included in the control group. Serum LOX-1 level was detected on admission, immediately after PCI or CAG and 1 week after PCI (only ACS and SAP group) by ELISA method. 2. The second part of this study was done including additional cases, a total of 170 cases confirmed by CAG were included in the CAD group and 140 healthy subjects confirmed by CAG were included in the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the polymorphism of 3'-UTR 188 site of OLR1 gene. The gene distribution was compared between the two groups and their relationships with coronary artery disease were studied.Results:1.There were remarkable statistical difference in the level of sLOX-1 between ACS and SAP group on admission and immediately after PCI(P<0.05),and so was it between SAP group and control group(P<0.05). However, there was no statistical difference between ACS and SAP group in one week after PCI(P>0.05). Similarly there was no statistical difference of sLOX-1 between immediately after PCI and that before PCI in each group. The level of sLOX-1 tended to be decrease in one week after PCI as compared to that before PCI,but there was no statistical difference(P>0.05).2.There were three genotypes of the 3'-UTR 188 site of OLR1 gene:CC,CT and TT.In the CAD group the genotype frequencies of CC,CT and TT were 47.65%,42.35% and 10.00% respectively;in the control group the genotype frequencies were 54.29%,36.43% and 9.28% respectively;there was no significant difference between the two groups of genotype frequencies byχ2 test(P>0.05).C allele frequencies at 188 site were 68.82% in the CAD group and 72.50% in the control group while T allele frequencies at 188 site were 31.18% in the CAD group and 27.50% in the control group,there was no significant difference between this two groups byχ2 test(P>0.05).3. This study showed that the CC, CT+TT genotype corresponding to their serum level of sLOX-1 in the CAD group were 193.09±35.80μg/L and 208.03±45.84μg/L respectively; the CC, CT+TT genotype corresponding to their serum level of sLOX-1 in the control group were 144.53±30.02μg/L and 164.39±19.36μg/L respectively.The genotypes corresponding to their serum level of sLOX-1 within each group showed no significant difference (P>0.05).Conclusions:1. Patients with coronary artery disease have increased serum level of LOX-1, suggesting the increased level of oxidative modification of LDL; and oxidative modification in patients with ACS is significantly increased compared with that in patients with SAP, which infers LOX-1 expression might be higher in unstable plaques than in stable plaques, suggesting that LOX-1 is associated with the formation of unstable plaque, which might be used to predict as a serum marker of unstable plaque.2. Serum level of LOX-1 may be affected by mechanical damage and ischemia-reperfusion injury, these injuries may lead to the increased serum level of LOX-1.3. Serum level of LOX-1 is unrelated to the number of coronary vessel, and so it cannot be used as a reference index of the severity of coronary artery disease.4. There is no significant correlation between the polymorphism of 3'-UTR 188 site of OLR1 gene and coronary artery disease, therefore the polymorphism can not be confirmed as a predictor of coronary artery disease in the population.5. The serum level of LOX-1 is not related to the polymorphism of 3'-UTR 188 site of OLR1 gene.
Keywords/Search Tags:coronary artery disease, acute coronary syndrome, lectin-like oxidized low-density lipoprotein receptor-1, percutaneous coronary intervention, single nucleotide polymorphism
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