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      The role of common variants of the cholesteryl ester transfer protein gene in left main coronary artery disease

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          Abstract

          Background

          The cholesteryl ester transfer protein (CETP) has a central role in the lipid metabolism and therefore may alter the susceptibility to atherosclerosis.

          Methods

          The DNA of 471 subjects [133 subjects with angiographically documented left main coronary artery disease (LMCAD), 241 subjects with more peripheral coronary artery disease (MPCAD) and 97 subjects self reported healthy (Controls)] was analyzed for the frequency of TaqIB and I405V polymorphisms in the gene coding CETP.

          Results

          There is no significant difference in CETP allele frequency or genotype distribution among LMCAD and MPCAD patients although there is statistical difference between LMCAD and Controls (p = 0.001). Specifically, patients with LMCAD and B1B1 genotype of TaqIB polymorphism were more frequent present compared to Controls (33.8% vs 22.9%, respectively). The frequency of B2B2 genotype was 3 times lower in the LMCAD group compared to Controls (10.5% vs 30.2%, respectively). In the LMCAD group the frequency of B1 allele compared to Controls was higher (62% vs 46%, respectively, p = 0.001). The relationship between TaqIB gene polymorphism and the LMCAD was independent of lipid profile, with the exception of apolipoprotein A.

          Conclusions

          These findings indicate that the TaqIB polymorphism may have potential importance in screening individuals at high risk for developing CAD. However, this polymorphism cannot distinguish between LMCAD and MPCAD. Further prospective investigations in larger populations are required to confirm these findings.

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          Most cited references36

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          Genetic susceptibility to death from coronary heart disease in a study of twins.

          A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins. The study population consisted of 3298 monozygotic and 5964 dizygotic male twins and 4012 monozygotic and 7730 dizygotic female twins. The age at which one twin died of coronary heart disease was used as the primary independent variable to predict the risk of death from coronary heart disease in the other twin. Information about other risk factors was obtained from questionnaires administered in 1961 and 1963. Actuarial life-table analysis was used to estimate the cumulative probability of death from coronary heart disease. Relative-hazard estimates were obtained from a multivariate survival analysis. Among the men, the relative hazard of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 years, as compared with the hazard when one's twin did not die before 55, was 8.1 (95 percent confidence interval, 2.7 to 24.5) for monozygotic twins and 3.8 (1.4 to 10.5) for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative hazard was 15.0 (95 percent confidence interval, 7.1 to 31.9) for monozygotic twins and 2.6 (1.0 to 7.1) for dizygotic twins. Among both the men and the women, whether monozygotic or dizygotic twins, the magnitude of the relative hazard decreased as the age at which one's twin died of coronary heart disease increased. The ratio of the relative-hazard estimate for the monozygotic twins to the estimate for the dizygotic twins approached 1 with increasing age. These relative hazards were little influenced by other risk factors for coronary heart disease. Our findings suggest that at younger ages, death from coronary heart disease is influenced by genetic factors in both women and men. The results also imply that the genetic effect decreases at older ages.
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            Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.

            Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. Inception cohort study. Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.
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              Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.

              A low plasma level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary heart disease (CHD). A secondary prevention study, the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), demonstrated that CHD events were significantly reduced during a median follow-up of 5.1 years by treating patients with the fibric acid derivative gemfibrozil when the predominant lipid abnormality was low HDL-C. To determine if the reduction in major CHD events with gemfibrozil in VA-HIT could be attributed to changes in major plasma lipid levels. Multicenter, randomized, double-blind, placebo-controlled trial conducted from September 1991 to August 1998. The Department of Veterans Affairs Cooperative Studies Program, in which 20 VA medical centers were participating sites. A total of 2531 men with a history of CHD who had low HDL-C levels (mean, 32 mg/dL [0.83 mmol/L] ) and low low-density lipoprotein cholesterol (LDL-C) levels (mean, 111 mg/dL [2.88 mmol/L]). Participants were randomly assigned to receive gemfibrozil, 1200 mg/d (n = 1264), or matching placebo (n = 1267). Relation of lipid levels at baseline and averaged during the first 18 months of gemfibrozil treatment with the combined incidence of nonfatal myocardial infarction and CHD death. Concentrations of HDL-C were inversely related to CHD events. Multivariable Cox proportional hazards analysis showed that CHD events were reduced by 11% with gemfibrozil for every 5-mg/dL (0.13-mmol/L) increase in HDL-C (P =.02). Events were reduced even further with gemfibrozil beyond that explained by increases in HDL-C values, particularly in the second through fourth quintiles of HDL-C values during treatment. During gemfibrozil treatment, only the increase in HDL-C significantly predicted a lower risk of CHD events; by multivariable analysis, neither triglyceride nor LDL-C levels at baseline or during the trial predicted CHD events. Concentrations of HDL-C achieved with gemfibrozil treatment predicted a significant reduction in CHD events in patients with low HDL-C levels. However, the change in HDL-C levels only partially explained the beneficial effect of gemfibrozil.
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                Author and article information

                Journal
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2011
                7 September 2011
                : 10
                : 156
                Affiliations
                [1 ]1st Cardiology Department, Onassis Cardiac Surgery Center 356, Sygrou Ave., 176 74 Athens, Greece
                [2 ]Molecular Immunology Laboratory, Onassis Cardiac Surgery Center 356, Sygrou Ave., 176 74 Athens, Greece
                [3 ]Thriasio General Hospital, Genimata Ave., 19600 Magoula, Attiki, Greece
                [4 ]Tzaneio Hospital,18536 Piraeus, Greece
                Article
                1476-511X-10-156
                10.1186/1476-511X-10-156
                3175181
                21899732
                53ee5e63-bf47-4f7a-aac4-5bb5ebc06600
                Copyright ©2011 Kolovou et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 July 2011
                : 7 September 2011
                Categories
                Research

                Biochemistry
                left main coronary artery disease,taqib polymorphism,i405v polymorphism.,atherosclerosis

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