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Jean-charles Fruchart - One of the best experts on this subject based on the ideXlab platform.
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Glucose regulates the expression of the Apolipoprotein A5 gene.
Journal of molecular biology, 2008Co-Authors: Maxime Nowak, Len A. Pennacchio, Audrey Helleboid-chapman, Jamila Fruchart-najib, Heidelinde Jakel, Emmanuelle Moitrot, Corinne Rommens, Jean-charles FruchartAbstract:The Apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.
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Is Apolipoprotein A5 a novel regulator of triglyceride‐rich lipoproteins?
Annals of medicine, 2006Co-Authors: Heidelinde Jakel, Audrey Helleboid-chapman, Jamila Fruchart-najib, Maxime Nowak, Jean-charles FruchartAbstract:Hypertriglyceridemia is an independent risk factor for the development of cardiovascular disease and is often associated with diabetes, inflammation and the metabolic syndrome. Recently, Apolipoprotein A5 (APOA5) was identified as a novel member of the APOA1/C3/A4 gene cluster. Data from mice over‐expressing or lacking APOA5 provide direct evidence that this Apolipoprotein plays a role in triglyceride metabolism. Moreover, plasma triglyceride levels were found to be strongly associated with APOA5 polymorphisms. The human APOA5 gene is regulated by transcription factors known to affect triglyceride metabolism such as PPARα, RORα, LXR and SREBP‐1c and this supports its function. Insulin and interleukins regulate APOA5 gene expression and provide novel clues for the role of this Apolipoprotein. To date, the triglyceride lowering action of apoA‐V is attributed to the activation of lipoprotein lipase and an acceleration of very low density lipoprotein catabolism. Recent findings indicate that APOA5 could also ...
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is Apolipoprotein A5 a novel regulator of triglyceride rich lipoproteins
Annals of Medicine, 2006Co-Authors: Heidelinde Jakel, Maxime Nowak, Audrey Helleboidchapman, Jamila Fruchartnajib, Jean-charles FruchartAbstract:Hypertriglyceridemia is an independent risk factor for the development of cardiovascular disease and is often associated with diabetes, inflammation and the metabolic syndrome. Recently, Apolipoprotein A5 (APOA5) was identified as a novel member of the APOA1/C3/A4 gene cluster. Data from mice over‐expressing or lacking APOA5 provide direct evidence that this Apolipoprotein plays a role in triglyceride metabolism. Moreover, plasma triglyceride levels were found to be strongly associated with APOA5 polymorphisms. The human APOA5 gene is regulated by transcription factors known to affect triglyceride metabolism such as PPARα, RORα, LXR and SREBP‐1c and this supports its function. Insulin and interleukins regulate APOA5 gene expression and provide novel clues for the role of this Apolipoprotein. To date, the triglyceride lowering action of apoA‐V is attributed to the activation of lipoprotein lipase and an acceleration of very low density lipoprotein catabolism. Recent findings indicate that APOA5 could also ...
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Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor RORα
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Annelise Genoux, Len A. Pennacchio, Hélène Dehondt, Audrey Helleboid-chapman, Christian Duhem, Dean W. Hum, Geneviève Martin, Bart Staels, Jamila Fruchart-najib, Jean-charles FruchartAbstract:Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoA5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis
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Transcriptional Regulation of Apolipoprotein A5 Gene Expression by theNuclear Receptor ROR alpha
Lawrence Berkeley National Laboratory, 2004Co-Authors: Annelise Genoux, Len A. Pennacchio, Hélène Dehondt, Audrey Helleboid-chapman, Christian Duhem, Dean W. Hum, Geneviève Martin, Bart Staels, Jamila Fruchart-najib, Jean-charles FruchartAbstract:Author(s): Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles | Abstract: Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoA5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis
Jong Ho Lee - One of the best experts on this subject based on the ideXlab platform.
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Association of Apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men
Atherosclerosis, 2008Co-Authors: Yae Jung Hyun, Yangsoo Jang, Jey Sook Chae, Ji-young Kim, Jean Kyung Paik, So Yeon Kim, Ju Young Yang, Jose M. Ordovas, Jong Ho LeeAbstract:Objective Whereas the relation between Apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting of a case–control study involving Korean males.
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The −1131T→C polymorphism in the Apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men
The American journal of clinical nutrition, 2004Co-Authors: Yangsoo Jang, Ji-young Kim, Jose M. Ordovas, Oh Yoen Kim, Jong Eun Lee, Hongkeun Cho, Jong Ho LeeAbstract:Background: Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. Objective: The objective was to determine associations of the common Apolipoprotein A5 gene (APOA5) 1131T3 C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in humans. Design: Healthy, nonobese subjects [n 158; mean (SEM) age: 33.8 1.2 y; body mass index (in kg/m 2 ): 23.3 0.3] were subdivided into 3 genotype groups: TT (n 85), TC (n 56), and CC (n 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. Results: Fasting triacylglycerol concentrations in carriers of the C allele were higher (P 0.05) than in carriers of the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal, carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F2 concentrations and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty acid measures. Conclusions: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5gene polymorphism and extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in Koreans independently of common environmental factors. Am J Clin Nutr 2004;80:832– 40.
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the 1131t c polymorphism in the Apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia elevated small dense ldl concentrations and oxidative stress in nonobese korean men
The American Journal of Clinical Nutrition, 2004Co-Authors: Yangsoo Jang, Ji-young Kim, Jose M. Ordovas, Oh Yoen Kim, Jong Eun Lee, Hongkeun Cho, Jong Ho LeeAbstract:Background: Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. Objective: The objective was to determine associations of the common Apolipoprotein A5 gene (APOA5) 1131T3 C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in humans. Design: Healthy, nonobese subjects [n 158; mean (SEM) age: 33.8 1.2 y; body mass index (in kg/m 2 ): 23.3 0.3] were subdivided into 3 genotype groups: TT (n 85), TC (n 56), and CC (n 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. Results: Fasting triacylglycerol concentrations in carriers of the C allele were higher (P 0.05) than in carriers of the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal, carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F2 concentrations and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty acid measures. Conclusions: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5gene polymorphism and extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in Koreans independently of common environmental factors. Am J Clin Nutr 2004;80:832– 40.
Shui-ping Zhao - One of the best experts on this subject based on the ideXlab platform.
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Emerging evidences for the opposite role of Apolipoprotein C3 and Apolipoprotein A5 in lipid metabolism and coronary artery disease.
Lipids in health and disease, 2019Co-Authors: Wen Dai, Ziyu Zhang, Chun Yao, Shui-ping ZhaoAbstract:Apolipoprotein C3 (apoC3) and Apolipoprotein A5 (apoA5), encoded by APOA1/C3/A4/A5 gene cluster, are two critical regulators of plasma triglyceride (TG) metabolism. Deficiency of apoC3 or apoA5 led to significant decreased or increased plasma TG levels, respectively. Recent studies indicated apoC3 and apoA5 also played roles in plasma remnant cholesterol, high density lipoprotein (HDL) and hepatic TG metabolisms. Moreover, large scale population genetic studies indicated that loss of function mutations in APOC3 and APOA5 gene conferred decreased and increased risk of coronary artery disease (CAD), respectively. This manuscript mainly reviewed existing evidences suggesting the opposite role of apoC3 and apoA5 in lipid metabolism and CAD risk, and discussed the potential correlation between these two Apolipoproteins.
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Apolipoprotein A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2018Co-Authors: Yaqiong Liu, Wang Zhao, Shui-ping ZhaoAbstract:Apolipoprotein A5 (Apo A5) is a novel member in Apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.
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Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the Apolipoprotein A5 pathway.
Biochemical and biophysical research communications, 2016Co-Authors: Lu-zhu Chen, Shui-ping Zhao, Wang Zhao, Xian-sheng HuangAbstract:Abstract Introduction Apolipoprotein A5 (apoA5) is a key regulator of triglyceride (TG) metabolism. This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions. Methods Two obese mouse models, including high-fat diet-induced obese mice and ob/ob obese mice, were adopted. The effects of low- and high-dose metformin were determined on plasma and hepatic TG and apoA5 of these obese mice. Besides, the effects of metformin on TG and apoA5 were also detected in mouse and human hepatocytes in vitro . Results (1) Plasma apoA5 levels in the obese mice were markedly elevated and positively correlated with TG. Hepatic TG contents and apoA5 expressions were also remarkably increased in the obese mice. (2) Metformin dose-dependently decreased hepatic and plasma TG and apoA5 in the obese mice. Similarly, metformin dose-dependently reduced cellular TG contents and apoA5 expressions in hepatocytes in vitro . Compared to APOA5 knock-down (KD), metformin plus APOA5 KD resulted in more TG reduction of hepatocytes. Conclusion Increased hepatic and plasma apoA5 could be a result of obesity-associated hypertriglyceridemia, and metformin displays hypotriglyceridemic effects on obese mice partly via the apoA5 pathway.
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The influence of statin-fibrate combination therapy on lipids profile and Apolipoprotein A5 in patients with acute coronary syndrome
Lipids in health and disease, 2013Co-Authors: Hai-rong Gong, Xian-sheng Huang, Wen-yu Huang, Shui-ping ZhaoAbstract:Background Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome (ACS) complicated by elevated triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C). The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and Apolipoprotein A5 (apoA5) level in patients with ACS.
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The role of Apolipoprotein A5 in obesity and the metabolic syndrome
Biological reviews of the Cambridge Philosophical Society, 2012Co-Authors: Xiao-yan Zheng, Shui-ping Zhao, Hu YanAbstract:Apolipoprotein A5 (apoA5) has an important role in lipid metabolism, specifically for triglyceride-rich lipoproteins. Recently, evidence has emerged for an association between genetic variability at the APOA5 locus and increased risk of obesity and metabolic syndrome. However, its mechanism of action remains to be fully elucidated. Importantly, an intracellular role of apoA5 has been indicated since apoA5 is associated with cytoplasmic lipid droplets and affects intrahepatic triglyceride accumulation, as well as affecting intravascular triglyceride metabolism. Given that adipocytes provide the largest storage depot for energy in the form of triglyceride within the lipid droplets, and play a crucial role in the development of obesity, we highlight recent findings discussing the interaction of apoA5 with adipocytes or adipose tissue, indicating that apoA5 may act as a novel regulator to modulate triglyceride storage in adipocytes. We review the association of APOA5 gene polymorphisms with obesity and metabolic syndrome, and propose potential mechanisms by which apoA5 may increase susceptibility to these conditions. This review provides new insights into the physiological role of apoA5 and identifies a potential therapeutic target for obesity and associated disorders.
Len A. Pennacchio - One of the best experts on this subject based on the ideXlab platform.
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Glucose regulates the expression of the Apolipoprotein A5 gene.
Journal of molecular biology, 2008Co-Authors: Maxime Nowak, Len A. Pennacchio, Audrey Helleboid-chapman, Jamila Fruchart-najib, Heidelinde Jakel, Emmanuelle Moitrot, Corinne Rommens, Jean-charles FruchartAbstract:The Apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.
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Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor RORα
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Annelise Genoux, Len A. Pennacchio, Hélène Dehondt, Audrey Helleboid-chapman, Christian Duhem, Dean W. Hum, Geneviève Martin, Bart Staels, Jamila Fruchart-najib, Jean-charles FruchartAbstract:Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoA5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis
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Transcriptional Regulation of Apolipoprotein A5 Gene Expression by theNuclear Receptor ROR alpha
Lawrence Berkeley National Laboratory, 2004Co-Authors: Annelise Genoux, Len A. Pennacchio, Hélène Dehondt, Audrey Helleboid-chapman, Christian Duhem, Dean W. Hum, Geneviève Martin, Bart Staels, Jamila Fruchart-najib, Jean-charles FruchartAbstract:Author(s): Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles | Abstract: Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoA5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis
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Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice
Arteriosclerosis thrombosis and vascular biology, 2004Co-Authors: Nadine Baroukh, Edward M. Rubin, Jamila Fruchart-najib, Jean-charles Fruchart, Eric Bauge, Jennifer A. Akiyama, Jessie Chang, Veena Afzal, Len A. PennacchioAbstract:Objective— Both the Apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are strongly altered by changes in the expression of either of these 2 genes. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. These similar findings raised the issue of the relationship between these 2 genes and altered triglycerides. Methods and Results— To address this issue, we generated independent lines of mice that either overexpressed (“double transgenic”) or completely lacked (“double knockout”) both Apolipoprotein genes. We report that both “double transgenic” and “double knockout” mice display normal triglyceride concentrations compared with overexpression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the “double transgenic” mice are ≈500-fold lower than human ApoCIII levels, supporting ApoAV as a potent triglyceride modulator despite its low concentration. Conclusions— Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.
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Phosphorylation-dependent down-regulation of Apolipoprotein A5 by insulin
Molecular and Cellular Biology, 2004Co-Authors: Maxine Nowak, Len A. Pennacchio, Edward M. Rubin, Audrey Helleboid-chapman, Geneviève Martin, Bart Staels, Heidelinde Jakel, Corinne Rommens, Daniel Duran-sandoval, Marja-riitta TaskinenAbstract:The Apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.
Jose M. Ordovas - One of the best experts on this subject based on the ideXlab platform.
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Association of Apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men
Atherosclerosis, 2008Co-Authors: Yae Jung Hyun, Yangsoo Jang, Jey Sook Chae, Ji-young Kim, Jean Kyung Paik, So Yeon Kim, Ju Young Yang, Jose M. Ordovas, Jong Ho LeeAbstract:Objective Whereas the relation between Apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting of a case–control study involving Korean males.
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Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Healthy Caucasian Population
The Journal of clinical endocrinology and metabolism, 2007Co-Authors: Rafael Moreno-luna, Francisco Perez-jimenez, Carmen Marin, Pablo Perez-martinez, Purificación Gómez, Yolanda Jimenez-gomez, Javier Delgado-lista, Juan Antonio Moreno, Toshiko Tanaka, Jose M. OrdovasAbstract:Background: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. Design and Methods: Eighty-eight APO E3/3 volunteers [67 with (−1131T and 56C) APOA5*1 haplotype, 12 with (−1131C and 56C) APOA5*2 haplotype, and nine with (−1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, Apolipoprotein B-100, Apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. Results: Subjects with the APOA5*2 and...
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The −1131T→C polymorphism in the Apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men
The American journal of clinical nutrition, 2004Co-Authors: Yangsoo Jang, Ji-young Kim, Jose M. Ordovas, Oh Yoen Kim, Jong Eun Lee, Hongkeun Cho, Jong Ho LeeAbstract:Background: Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. Objective: The objective was to determine associations of the common Apolipoprotein A5 gene (APOA5) 1131T3 C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in humans. Design: Healthy, nonobese subjects [n 158; mean (SEM) age: 33.8 1.2 y; body mass index (in kg/m 2 ): 23.3 0.3] were subdivided into 3 genotype groups: TT (n 85), TC (n 56), and CC (n 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. Results: Fasting triacylglycerol concentrations in carriers of the C allele were higher (P 0.05) than in carriers of the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal, carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F2 concentrations and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty acid measures. Conclusions: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5gene polymorphism and extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in Koreans independently of common environmental factors. Am J Clin Nutr 2004;80:832– 40.
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the 1131t c polymorphism in the Apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia elevated small dense ldl concentrations and oxidative stress in nonobese korean men
The American Journal of Clinical Nutrition, 2004Co-Authors: Yangsoo Jang, Ji-young Kim, Jose M. Ordovas, Oh Yoen Kim, Jong Eun Lee, Hongkeun Cho, Jong Ho LeeAbstract:Background: Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. Objective: The objective was to determine associations of the common Apolipoprotein A5 gene (APOA5) 1131T3 C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in humans. Design: Healthy, nonobese subjects [n 158; mean (SEM) age: 33.8 1.2 y; body mass index (in kg/m 2 ): 23.3 0.3] were subdivided into 3 genotype groups: TT (n 85), TC (n 56), and CC (n 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. Results: Fasting triacylglycerol concentrations in carriers of the C allele were higher (P 0.05) than in carriers of the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal, carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F2 concentrations and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty acid measures. Conclusions: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5gene polymorphism and extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in Koreans independently of common environmental factors. Am J Clin Nutr 2004;80:832– 40.