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      Association between Single Nucleotide Polymorphism rs1044925 and the Risk of Coronary Artery Disease and Ischemic Stroke

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          Abstract

          The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 ( ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls ( p = 0.015) and borderline different between the IS patients and controls ( p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.

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          Most cited references 39

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          Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults.

           ,  Bei Zhou (2002)
          For prevention of obesity in Chinese population, it is necessary to define the optimal range of healthy weight and the appropriate cut-off points of BMI and waist circumference for Chinese adults. The Working Group on Obesity in China under the support of International Life Sciences Institute Focal point in China organized a meta-analysis on the relation between BMI, waist circumference and risk factors of related chronic diseases (e.g., high diabetes, diabetes mellitus, and lipoprotein disorders). 13 population studies in all met the criteria for enrollment, with data of 239,972 adults (20-70 year) surveyed in the 1990s. Data on waist circumference was available for 111,411 persons and data on serum lipids and glucose were available for more than 80,000. The study populations located in 21 provinces, municipalities and autonomous regions in mainland China as well as in Taiwan. Each enrolled study provided data according to a common protocol and uniform format. The Center for data management in Department of Epidemiology, Fu Wai Hospital was responsible for statistical analysis. The prevalence of hypertension, diabetes, dyslipidemia and clustering of risk factors all increased with increasing levels of BMI or waist circumference. BMI at 24 with best sensitivity and specificity for identification of the risk factors, was recommended as the cut-off point for overweight, BMI at 28 which may identify the risk factors with specificity around 90% was recommended as the cut-off point for obesity. Waist circumference beyond 85 cm for men and beyond 80 cm for women were recommended as the cut-off points for central obesity. Analysis of population attributable risk percent illustrated that reducing BMI to normal range ( or = 28) with drugs could prevent 15%-17% clustering of risk factors. The waist circumference controlled under 85 cm for men and under 80 cm for women, could prevent 47%-58% clustering of risk factors. According to these, a classification of overweight and obesity for Chinese adults is recommended.
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            Acyl-coenzyme A:cholesterol acyltransferases.

            The enzymes acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs) are membrane-bound proteins that utilize long-chain fatty acyl-CoA and cholesterol as substrates to form cholesteryl esters. In mammals, two isoenzymes, ACAT1 and ACAT2, encoded by two different genes, exist. ACATs play important roles in cellular cholesterol homeostasis in various tissues. This chapter summarizes the current knowledge on ACAT-related research in two areas: 1) ACAT genes and proteins and 2) ACAT enzymes as drug targets for atherosclerosis and for Alzheimer's disease.
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              The forgotten majority: unfinished business in cardiovascular risk reduction.

               Peter Libby (2005)
              Despite meaningful progress in the identification of risk factors and the development of highly effective clinical tools, deaths from cardiovascular disease continue to increase worldwide. Sparked by an obesity epidemic, the metabolic syndrome and the rising incidence of type 2 diabetes have led to an upsurge of cardiovascular risk. Although pharmacologic treatments with the statin class of drugs have reduced cholesterol levels and lowered mortality rates, several large controlled clinical trials, including the Scandinavian Simvastatin Survival Study, the Cholesterol and Recurrent Events trial, the Air Force/Texas Coronary Atherosclerosis Prevention studies, and Long-term Intervention with Pravastatin in Ischemic Disease study, have indicated that cardiovascular events continue to occur in two thirds of all patients. Follow-up studies, such as the Heart Protection Study and the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis In Myocardial Infarction-22 trials, reinforced these earlier results. Although therapy with gemfibrozil, a fibric acid derivative, showed reduced occurrence of cardiovascular events in the Helsinki Heart Study and the Veterans Affairs HDL Intervention Trial, results of other studies, e.g., the Bezafibrate Intervention Program and the Diabetes Atherosclerosis Intervention study, showed less encouraging results. Although lifestyle modifications, such as improved diet and increased exercise levels, benefit general health and the metabolic syndrome and insulin resistance in particular, most people continue to resist changes in their daily routines. Thus, physicians must continue to educate their patients regarding an optimal balance of drug therapy and personal behavior.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                March 2014
                26 February 2014
                : 15
                : 3
                : 3546-3559
                Affiliations
                [1 ]Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; E-Mails: wulove26@ 123456tom.com (D.-F.W.); nncwx@ 123456163.com (W.-X.C.)
                [2 ]Department of Neurology, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; E-Mail: maten1996@ 123456gmail.com
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: yinruixing@ 123456163.com ; Tel.: +86-771-532-6125; Fax: +86-771-535-3342.
                Article
                ijms-15-03546
                10.3390/ijms15033546
                3975353
                24577316
                © 2014 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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