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      The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women

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          Abstract

          Background

          The APOA5 rs662799 polymorphism has been widely reported regarding its associations with the plasma lipid levels and the occurrence of coronary heart disease (CHD), whereas its relationship with the severity of CHD has not yet been explored.

          Methods

          Four hundred and seventy-eight angiografically defined subjects (325 CHD patients and 153 CHD-free controls) were enrolled in this study. The rs662799 polymorphism was genotyped, and the fasting lipid data were collected for all participants. The severity of CHD was evaluated for the CHD patients by using Gensini scores.

          Results

          The variant C allele of the rs662799 polymorphism was associated with lower levels of HDL-C in CHD-free women, and higher levels of TG and TG/HDL-C in women with CHD ( P < 0.05 for all). The C allele was associated with higher prevalence of dyslipidemia and higher levels of Gensini scores only in women ( P < 0.05 for both), but not in men. Multivariate linear regression analysis showed that the rs662799 polymorphism was independently associated with the Gensini scores in women after adjustment for other potential CHD risk factors (Beta = 0.157, 95 % CI: 0.017–0.298, P = 0.028).

          Conclusion

          Our data indicate that the rs662799 polymorphism is associated with dyslipidemia and the severity of CHD in Chinese women.

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          Most cited references27

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          An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.

          Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.
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            Status of cardiovascular health in Chinese adults.

            Cardiovascular disease has become the leading cause of death in China.
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              ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.

              ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 10(8) plaqueforming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins.
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                Author and article information

                Contributors
                +86 817 3352032 , songyongyan2014@foxmail.com
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                30 September 2016
                30 September 2016
                2016
                : 15
                : 170
                Affiliations
                [1 ]Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000 China
                [2 ]School of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000 China
                [3 ]Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, 68583-0806 NE USA
                [4 ]Department of Radiology, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000 China
                [5 ]Department of Medical Biochemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong, 637000 China
                Article
                343
                10.1186/s12944-016-0343-z
                5054624
                27716220
                e0d43309-1be9-43c2-9570-dc5f86071dd3
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 March 2016
                : 22 September 2016
                Funding
                Funded by: the Basic and Applied Research Project of Sichuan Province, China
                Award ID: 2013JY0072
                Award Recipient :
                Funded by: the Key Cultivation Project of North Sichuan Medical College, Sichuan Province, China
                Award ID: CBY12-A-ZP06
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Biochemistry
                apoa5,rs662799,coronary heart disease,lipid,severity
                Biochemistry
                apoa5, rs662799, coronary heart disease, lipid, severity

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