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      Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy

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          Abstract

          Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)- HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m 2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.

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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.

          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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            Foam cells in atherosclerosis.

            Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1(ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export. When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plaque. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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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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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                19 January 2018
                19 January 2018
                28 February 2018
                : 38
                : 1
                : BSR20171058
                Affiliations
                [1 ]Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China
                [2 ]Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China
                Author notes
                Correspondence: Rui-Xing Yin ( yinruixing@ 123456163.com ) or Yu-Ming Chen ( yumchen@ 123456163.com )
                Article
                10.1042/BSR20171058
                5773822
                29208769
                3f77b64a-ba2a-4ed3-a21b-f855777d371f
                © 2018 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 28 July 2017
                : 21 November 2017
                : 04 December 2017
                Page count
                Pages: 15
                Categories
                Research Articles
                Research Article
                40
                7
                48

                Life sciences
                coronary heart disease,genetic variants,hepatitis a virus cellular receptor 1,ischemic stroke,lipids,t-cell immunoglobulin domain and mucin domain 4

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