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Genetic risk factors for arterial vascular disease

Author: LiWenLong
Tutor: HuiRuTai;PeiWeiDong;ZhouXianLiang;HuangXiaoHong;ChenJingZhou;WangHu
School: Peking Union Medical College , China
Course: Genetics
Keywords: Cyclooxygenase- 2 Coronary heart disease Lymphotoxin Galectin Monocyte chemoattractant protein Polymorphism D-dimer Acute aortic dissection Diagnosis
CLC: R543
Type: PhD thesis
Year: 2010
Downloads: 147
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Abstract


Background: coronary heart disease and ischemic stroke is a serious impact on human health diseases. Atherosclerosis is a common pathological basis of coronary heart disease and ischemic stroke. Inflammatory factors play an important role in the occurrence and development of atherosclerosis. Cyclooxygenase 2 (of cyclooxygenase-2, COX-2) is a synthetic prostaglandin, prostacyclin and thromboxane important protein. Prostaglandins and thromboxane involved in the development and progression of coronary heart disease and stroke. Lymphotoxin-a (Lymphotoxin-a) and galectin of -2 (galectin-2) is important proinflammatory cytokines play an important role in the occurrence and development of coronary atherosclerosis. Monocyte chemoattractant protein -1 (Monocyte chemoattractant protein-1) expression in coronary atheroma, and is involved in the progression of atherosclerotic plaque. Previous studies suggest that cyclooxygenase-2 gene polymorphism (G-765C) is associated with coronary heart disease and ischemic stroke. Monocyte chemoattractant protein-1, lymphotoxin-a galectin 2 gene polymorphisms with coronary artery disease and myocardial infarction. However, other studies have failed to repeat the association. Objective and Methods: We evaluated case - control study and meta-analysis methods, COX-2 G-765C and coronary heart disease, ischemic stroke, LTA gene, LGALS2 gene with coronary heart disease, MCP-1 gene and acute myocardial infarction correlation. Search PubMed, EMBASE, CBM, CNKI database to find this association studies. Analyzed by two independent researchers, to extract data pooled OR (odds ratio) and 95% confidence interval. The analysis for the association of the MCP-1 gene with myocardial infarction, we selected 470 cases of myocardial infarction patients and 522 healthy controls. MCP-1 gene was detected by PCR-RFLP method 3 tag SNPs, rs1024611, rs3760399 and rs3760396, through case-control study and meta-analysis, correlation results to explore polymorphism and myocardial infarction: the COX-2 gene with coronary heart disease The meta-analysis included 4930 patients with coronary heart disease patients and 17,997 controls, 1628 cases of ischemic stroke patients and 17,653 controls. Coronary heart disease genetic pattern discovery recessive mode of inheritance,-765C of the combined OR was 0.80 (95% CI :0.65-0 .98, P = 0.03): the dominant mode of inheritance, pooled OR value of 0.99 (95% CI: 0.92- 1.06, P = 0.70). For ischemic stroke, recessive mode of inheritance,-765C pooled OR value of 1.11 (95% :0.88-1 .42, P = 0.38); dominant inheritance pattern, combined OR = 1.05 (95% CI :0.93-1 .18 , P = 0.42). No publication bias in this meta-analysis. Control subjects were enrolled in the LTA, LGALS-2 gene is associated with coronary heart disease analysis, 20 640 (LTA-A252G) and 10 552 (LGALS2-C3279T) patients, and 15 388 (A252G) and 10545 (C3279T). After the merger, the dominant mode of inheritance 252G combined OR = 1.02 (95% :0.97-1 .07, P = 0.41); recessive mode of inheritance, OR = 1.00 (95% :0.94-1 .07, P = 0.93). After the merger, the dominant mode of inheritance, 3279T pooled OR value of 0.95 (95% CI :0.89-1 .01, P = 0.07); recessive mode of inheritance, OR = 0.89 (95% CI :0.78-1 .00 = 0.06) . Not found rs1024611 (OR = 1.19:95% CI :0.84-1 .70, P = 0.31), rs3760399 (OR = 1.29:95% CI :0.91-1 .82, P = 0.13), rs3760396 (OR = 1.27:95% CI: 0.83-1.96, P = 0.23) and myocardial infarction associated. Meta-analysis including 1916 cases of myocardial infarction patients and 5538 healthy controls, the dominant mode of inheritance, the pooled OR value of 1.05 (95% CI 0.93 - 1 .18, P = 0.46); recessive mode of inheritance, the pooled OR value of 0.94 (95% CI, :0.80-1 .10, P = 0.41). Conclusion: This study found, COX-2-765C CAD protective factors, not associated with ischemic stroke; the LTA,-2 LGALS, MCP-1 gene polymorphism with CAD unrelated. Background: Acute aortic dissection is a rare fatal disease of the emergency room, and the mortality rate is high. D-dimer is a fibrin degradation products, often elevated in patients with acute aortic dissection. However, the diagnostic and predictive value of D-dimer in acute aortic dissection is unclear. Objective: This study evaluated the sensitivity of D-dimer in the disease, specificity, positive likelihood ratio, negative likelihood ratio, to explore the diagnosis and prognosis of D-dimer in acute aortic dissection aspects of the value. METHODS: We collected between January 2008 to December 2009, 202 cases of acute aortic dissection patients to the emergency room within 24 hours after onset. These patients are enhanced CT or MRI to confirm the diagnosis. Also included 584 patients with suspected acute aortic dissection in patients with acute myocardial infarction in 310 cases of angina 132 cases, 43 cases of pulmonary embolism and 95 cases of other diseases. Serum D-dimer level was measured using stago-evolution (France) (effective detection range of 0.22-20 ug / ml). Meta-analysis, analysis of the diagnosis of aortic dissection in level 0.5ug/ml, D-dimer sensitivity and specificity. Results: D-dimer levels in patients with acute aortic dissection was significantly higher (median 4.18 vs 0.45ug/ml P lt; 0.05). Stanford A patients (median 4.6 vs 3.64 ug / ml, P lt; 0.05), D-dimer levels increased significantly in patients with Stanford B type. Intramural hematoma in patients with D-dimer levels than typical in patients with aortic dissection significantly reduce (median 4.28 vs.3.6 ug / ml, P lt; 0.05). ROC curve, D-dimer is effectively exclude acute aortic dissection indicators, sensitivity 94%, specificity of 57.0%. When the D-dimer 0.5ug/ml negative likelihood ratio of 0.1, a positive likelihood ratio of 2.18. D-dimer levels between those who died and the survivors, there is no significant difference (median 4.13 vs.6.18ug/ml, P gt; 0.05). The meta-analysis found a sensitivity of 0.95 (95% CI :0.92-0.97, P = 0.06), a specificity of 0.54 (95% CI :0.51-0 .57, P lt; 0.05). Merge positive likelihood ratio of 1.98 (95% CI, :1.84-2 .12, I2 = 82.2%, P = 0.000), merge negative likelihood ratio of 0.10 (95% CI, :0.07-0 .15, I2 = 38.6%, P = 0.15 ). Conclusion: The onset within 24 hours of the D-dimer is the exclusion of acute aortic dissection indicators, but there is no correlation between hospital mortality.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease
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