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A Meta-analysis Of The Association Between ESR1 Genetic Polymorphism And Cardiovascular And Cerebrovascular Diseases

Posted on:2011-09-27Degree:MasterType:Thesis
Country:ChinaCandidate:X J WengFull Text:PDF
GTID:2144360305955111Subject:Epidemiology and Health Statistics
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ObjectiveEstrogen receptor is one of the nuclear receptor super families and widely distributed in most tissues and organs. Estrogens are important hormones that exert their actions via estrogen receptors that influence multiple organ systems, not only the reproductive system function, but also the cardiovascular system and the neuroendocrine system. We found the association between ESR1 gene polymorphism and cardiovascular disease, but the conclusions of studies were not entirely consistent, which may be due to small sample size or too limited scope of the single study. Meta analysis is a kind of statistical methods which is targeted to synthesize and analysis kinds of studies with the same specific conditions and subject. It can overcome the disadvantages of the single study, including the small sample size and the large variation of the result, to make the results more objective and to provide a stronger basis to propose a hypothesis by the method of the merger of a number of previous studies. A meta analysis was undertaken to review the evidence of an association between the ESR1 polymorphisms and the cardiovascular and cerebrovascular disease, to get more scientific and accurate conclusions for providing evidence-based clues to future research.MethodsA search in the PubMed, CNKI, Wanfang and Vip database from January 1997 to March 2010 was made. In accordance with the inclusion and exclusion criteria to retrieve publications and the same two reviewers independent assessed the quality of the publications. The data of basic information were extracted from the eligible studies, and the data were entered into a database and statistical analyses performed using RevMan software (version 5.0.21; Oxford, U.K.) with odds ratio (OR) as statistics. Selected effects model to combine OR on the basis of heterogeneity test results. Subgroup analysis were under by disease type, the race and gender type, and sensitivity analysis were under transform models, excluding the maximum weight of the studies, and also to remove the studies which control group wasn't in HWE. Use funnel plot to analyze publication bias.ResultsThere were 132 publications identified. Of these, 23 were suitable for inclusion, which including 21 case - control studies and 2 cohort studies. There are five studies of stroke and eighteen studies of coronary artery disease. There are thirteen studies which study in east of Asian, eight studies which study in Caucasian people and their descendants, and two which study in west of Asian. The study mainly involved two sites: rs2234693 which included 22 studies and rs9340799 which included 17 studies. There are 7659 patients and 13563 controls in all.It is different that the distribution of rs2234693 between patients with cardiovascular and cerebrovascular diseases and non-patients (for TT vs. CC, OR = 0.76, 95% CI: 0.63 ~ 0.91; for T vs. C, OR = 0.89, 95% CI: 0.82 ~ 0.97). The different is also found in the Asian population (for TT vs. CC, OR =0.68, 95% CI: 0.50 ~ 0.91), in male population (for TC vs. CC, OR = 0.76, 95% CI: 0.58 ~ 0.99; for TT vs. CC, OR = 0.67, 95% CI: 0.48 ~ 0.93, for T vs. C, OR = 0.83, 95% CI: 0.71 ~ 0.98), in the Asian men (for TC vs. CC, OR =0.65, 95% CI: 0.45 ~ 0.92; for TT vs. CC, OR = 0.57, 95% CI: 0.39 ~ 0.82), but it isn't found in Caucasus, female. Funnel plot showed that there is no published bias in all groups of people and women, but there is publication bias in study of male population.It is different that the distribution of rs2234693 between patients with coronary artery disease and non-patients (for TC vs. CC, OR = 0.88, 95% CI: 0.79~0.98; for TT vs. CC, OR = 0.71, 95% CI: 0.56~0.90; for T vs. C, OR =0.88, 95% CI: 0.79~0.99). The different is also found in the Asian population (for TC vs. CC, OR = 0.63, 95% CI: 0.42~0.95; for TT vs. CC, OR =0.66, 95% CI: 0.48~0.92), in the Asian men (for TT vs. CC, OR = 0.58, 95% CI: 0.38~0.88), but it isn't found in Caucasus, female. Funnel plot showed that there is no published bias in all groups of people and women, but there is publication bias in study of male population. It is no found that the association between stroke and rs2234693. But by the sensitivity analysis, it is found in the male population with removed the greatest weight study (for TT vs. CC, OR = 0.60, 95% CI: 0.38 ~ 0.93; for T vs. C, OR = 0.77, 95% CI: 0.61 ~ 0.96). And the studies included are only 5 articles, so it still can't make a definitive conclusion.It is no different that the distribution of rs9340799 between patients with cardiovascular disease and non-patients. The differences in Asia aren't significant; the sensitivity analysis shows that the results are not stable. It is the same in male. At the same time, it is no found that the association between coronary heart disease and rs9340799. But by the sensitivity analysis, it is found the association between GG genotype and coronary heart disease in Asian with removed the study which controls aren't in HWE. Funnel plot showed that there is no published bias in all groups of people and men, but there is publication bias in study of female population.ConclusionVariations wihin the rs2234693 cite in ESR1 gene are significantly assoiated with coronary heart disease, but not with stroke. It is reducing that the risk of coronary heart disease with the increasing number of T allele. In addition, variations wihin the r9340799 cite in ESR1 gene aren't assoiated with cardiovascular and cerebrovascular diseases. Racial and gender factors should be the influence factors of cardiovascular and cerebrovascular diseases. Rs9340799 variablility was confirmed to modulate susceptibility to coronary heart disease in Asian individuals, but not to stroke.
Keywords/Search Tags:ESR1, gene polymorphism, SNP, cardiovascular and cerebrovascular diseases, Meta analysis
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