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Green Tea Meta-analysis Of The Impact On Lipid Metabolism And The Lipa Genetic Variation And Risk Of Coronary Heart Disease Association Studies

Posted on:2013-01-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:X X ZhengFull Text:PDF
GTID:1114330374473757Subject:Internal Medicine
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Backgrounds:Coronary heart disease (CHD) remains a major disease as a threat to human health. Increased concentrations of serum total cholesterol (TC) and low density lipoprotein (LDL) cholesterol have been generally identified as the main risk factors for the occurrence of atherosclerosis and CHD. Previous studies have shown that the future risk of the occurrence of cardiovascular diseases can be reduced by30%when serum cholesterol levels are to be decreased by10%. A healthy lifestyle such as good eating habits can prevent the occurrence of hyperlipidemia. Green tea is a kind of daily drink without fermentation processing and is consumed widely. Green tea, originating in China, has been all over the world. Due to its no oxidation process, green tea can preserve its natural beneficial ingredients. Green tea mainly contains a variety of tea polyphenols including flavanols, flavonoids, phenolic acids, and so on, in which tea catechins, a kind of flavanols, is the most important material. Recent epidemiological studies suggest that green tea has cardiovascular protective effect and intake of green tea or green tea extract is associated with the decrease in the morbidity of cardiovascular disease. The large amount of basic research have proved that tea polyphenols (tea catechins) can inhibit the intestinal absorption of cholesterol, improve lecithin-cholesterol acyltransferase activity and high-density lipoprotein cholesterol levels, regulate apolipoprotein and lipoprotein levels, and accelerate the excretion of cholesterol, and thus green tea adjust the human body serum cholesterol level. Therefore, tea polyphenols can affect blood lipid profile levels.Previous clinical trials also suggest that drinking green tea or oral supplement of tea extract affects the adult fasting lipid levels. However, these clinical trials are mostly small sample sizes, and results are not consistent. Some clinical trials proved that drinking green tea or intaking orally green tea extract significantly reduced serum TC and LDL cholesterol levels and significantly elevated serum level of high density lipoprotein(HDL) cholesterol as well. However, other clinical trials showed that intake of green tea or its extracts had no significant effects on blood lipid levels. In brief, the effect of oral intake of green tea or its extract on lipid profile remains controversial. Objective:We systematically evaluate randomized controlled trials (RCT) which study the relationship between drinking green tea or oral supplement of green tea extract and serum levels of TC, LDL cholesterol, HDL cholesterol, aiming to identify and quantify the effect of green tea or its extract on lipid profile. We also investigate the possible intrinsic mechanism of the effect and provide theoretical basis for promoting a healthy lifestyle.Methods:We conducted a meta-analysis of randomized placebo-controlled green tea supplementation trials evaluating serum cholesterol. A comprehensive literature search through PubMed, Cochrane library, Embase, reviews, and reference lists of relevant papers published before March2011was performed in order to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Study quality was assessed using the Jadad score. In a fixed-effect model or random-effect model, using changes of lipid levels intervened by green tea or its extract as marked points, the weighted mean difference (WMD) and their95%confidence interval (CI) were used to calculate net changes of lipid (TC, LDL cholesterol and HDL cholesterol). Previously defined subgroup analysis and sensitivity analysis were performed to explore the influence of experimental factors or study characteristics.Results:Fourteen eligible RCTs with1,136subjects were enrolled and evaluated in the present meta-analysis. Since there was not long-term study, we focused on short-term effects of green tea. In an overall pooled estimate, green tea consumption significantly lowered TC by7.20mg/dL (95%CI,-8.19--6.21, P<0.001) and LDL cholesterol by2.19mg/dL (95%CI,-3.16--1.21, P<0.001). The mean change in blood HDL cholesterol concentration (increase in HDL cholesterol by0.25mg/dL,95%CI,-0.731.23,P=0.62) was not statistically significant. Subgroup analysis and sensitivity analysis demonstrated that these changes were not influenced by the type of intervention, treatment doses of green tea catechins, study duration, individual's health status, or the quality of the study. Overall, no significant heterogeneity was detected for TC (heterogeneity chi-square=14.30, I2=9.1%, P=0.353), LDL cholesterol (heterogeneity chi-square=13.41, I2=25.4%,P0.201), and HDL cholesterol (heterogeneity chi-square=13.36, I2=17.7%, P=0.270), and the results were reported based on fixed-effect models. Conclusions:Analysis of eligible studies revealed that short-term administration of green tea or its extracts effectively and significantly reduced serum total and LDL cholesterol concentrations, and no significant effect on HDL cholesterol was observed although intake of green tea or its extracts increased serum level of HDL cholesterol. The subgroup analysis further confirmed that the cholesterol-lowering effect of green tea and its extracts was not influenced of means of intervention, tea polyphenols dose, intervention time, the health status of the subjects, and included RCTs quality. Excluding low-quality intervention trials and conflicting interests, the sensitivity analysis showed that this cholesterol-lowering effect was not altered, which further confirmed the stability of the results of this meta-analysis. Backgrounds:Coronary artery disease (CAD), a complex and heterogeneous disease with a heritability exceeding50%, is one of the leading causes of morbidity and mortality both in China and in western society. Our knowledge of the factors involved in the etiology of CAD remains largely incomplete. The lipase A, lysosomal acid, cholesterol esterase enzyme (LIPA) is involved in the hydrolysis of triglycerides (TG) and cholesterol esters (CEs) delivered to lysosomes. As a critical enzyme for cleavage of CEs and TG delivered to the lysosomes via receptor-mediated endocytosis, LIPA plays a key role in supplying cholesterol. Dificient LIPA activity is associated with two inherited disorders of cholesterol metabolism, namely the Wolman disease (WD) and the CE storage disease (CESD). Individuals with WD show markedly elevated tissue levels of CE and TG. CESD is characterized by intracellular CE storage accompanied by a marginally abnormal intracellular accumulation of TG Patients with CESD demonstrate mild hypercholesterolemia, elevated low-density cholesterol levels and premature atherosclerosis. In the general population, a large proportion of coronary artery and cerebrovascular disease patients have low LIPA activity. According to the results of a genome-wide association study conducted in Europeans, LIPA was indentified as a susceptibility gene for CAD. We hypothesized that genetic variation in LIPA gene might alter the susceptibility to CAD in Chinese population.Objectives:In the present study, we investigated whether genetic variants in LIPA gene contributed to the risk of myocardial infarction.Methods:The hypothesis was tested in a case-control study. The SNPs were genotyped in568coronary artery disease patients and430control subjects. Genotype analyses were conducted for dominant models, additive models and recessive models.Results:Our results showed that the A allele of rs1412444was significantly associated with increased risk of coronary artery disease. Without adjustment of conventional risk factors, the crude odds ratios [ORs] were1.36(95%confidence interval [CI]:1.05to1.75, P=0.018) under dominant model,1.94(95%CI:1.27to2.95, P=0.002) under additive model and1.37(95%CI:1.13to1.66, P=0.001) under recessive model. After adjustment of conventional risk factors, the adjusted ORs were1.37(95%CI:1.01to1.88, P=0.046) under dominant model and1.30(95%CI:1.02to1.65, P=0.032) under recessive model.Conclusions:The present results indicate that variation in the gene LIPA is a genetic risk factor contributing to interindividual differences in coronary artery disease risk in Chinese Han population.
Keywords/Search Tags:green tea, tea catechins, cholesterol, randomized controlled trial, meta-analysisLIPA gene, SNP, variants, coronary artery disease
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