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https://www.readbyqxmd.com/read/29180722/rare-non-coding-variants-are-associated-with-plasma-lipid-traits-in-a-founder-population
#1
Catherine Igartua, Sahar V Mozaffari, Dan L Nicolae, Carole Ober
Founder populations are ideally suited for studies on the clinical effects of alleles that are rare in general populations but occur at higher frequencies in these isolated populations. Whole genome sequencing in 98 Hutterites, a founder population of European descent, and subsequent imputation revealed 660,238 single nucleotide polymorphisms that are rare (<1%) or absent in European populations, but occur at frequencies >1% in the Hutterites. We examined the effects of these rare in European variants on plasma lipid levels in 828 Hutterites and applied a Bayesian hierarchical framework to prioritize potentially causal variants based on functional annotations...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162127/association-of-the-s2-allele-of-the-ssti-polymorphism-in-the-apoc3-gene-with-plasma-apociii-interacts-with-unfavorable-lipid-profiles-to-contribute-to-atherosclerosis-in-the-li-ethnic-group-in-china
#2
Minzeng Sun, Lin Chen, Hui Liu, Lihui Ma, Tiansong Wang, Yueli Liu
BACKGROUND: The SstI polymorphism in the apolipoprotein 3 gene (apoC3) has been identified in many ethnic groups. In addition, the S2 allele of the SstI polymorphism is shown to be associated with increased plasma triglyceride (TG) levels. Plasma apoCIII is an important atherogenic factor, which interrupts lipid metabolism and is positively associated with plasma TG levels. However, the existence of the SstI polymorphism in the Li ethnic group in China remains to be confirmed. The relationship between the S2 allele of the SstI polymorphism and plasma apoCIII or TG and their roles in atherosclerosis are also unknown...
November 21, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29132372/hepatitis-b-virus-inhibits-the-in-vivo-and-in-vitro-synthesis-and-secretion-of-apolipoprotein-c3
#3
Chengliang Zhu, Hengcheng Zhu, Hui Song, Limin Xu, Longxuan Li, Fang Liu, Xinghui Liu
BACKGROUND: Hepatitis B virus (HBV) infection in the body can damage liver cells and cause disorders in blood lipid metabolism. Apolipoprotein C3 (ApoC3) plays an important role in the regulation of lipid metabolism, but no study on the HBV regulation of ApoC3 has been reported. This purpose of this study was to investigate the effect of HBV on ApoC3 expression and its regulatory mechanism. METHODS: The expression levels of ApoC3 mRNA and protein in the human hepatoma cell lines HepG2 and HepG2...
November 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29096837/the-role-of-antisense-oligonucleotide-therapy-against-apolipoprotein-ciii-in-hypertriglyceridemia
#4
Ioanna Gouni-Berthold
Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29081697/genetic-risk-factors-in-cerebrovascular-disorders-and-cognitive-deterioration
#5
Juan C Carril, Ramón Cacabelos
INTRODUCTION: The study of variations in genes involved in the different events that trigger the atherogenic process, such as lipid metabolism (modification of LDL-cholesterol), endothelial function and hypertension, immune response (recruitment of macrophages and foam cell formation) and stability of atherosclerotic plaques (thrombosis), established the risk for suffering a vascular disorder. A total of 2455 cases over 50 years of age were genotyped for a panel of 19 SNPs in 15 genes encoding for proteins involved in the atherogenic process...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/28948955/factors-affecting-high-density-lipoprotein-cholesterol-in-hiv-infected-patients-on-nevirapine-based-antiretroviral-therapy
#6
C Padmapriyadarsini, K Ramesh, L Sekar, Geetha Ramachandran, Devaraj Reddy, G Narendran, S Sekar, C Chandrasekar, D Anbarasu, Christine Wanke, Soumya Swaminathan
BACKGROUND & OBJECTIVES: Cardiovascular disease (CVD) risk with low high-density lipoprotein cholesterol (HDL-C) and high triglycerides is common in the general population in India. As nevirapine (NVP)-based antiretroviral therapy (ART) tends to increase HDL-C, gene polymorphisms associated with HDL-C metabolism in HIV-infected adults on stable NVP-based ART were studied. METHODS: A cross-sectional study was conducted between January 2013 and July 2014 among adults receiving NVP-based ART for 12-15 months...
May 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28919193/association-analysis-of-genetic-variants-with-metabolic-syndrome-components-in-the-moroccan-population
#7
F Lakbakbi El Yaagoubi, H Charoute, I Morjane, H Sefri, H Rouba, A Ainahi, M Kandil, H Benrahma, A Barakat
This study aimed to analyze the association between UBE2E2, G6PC2, PROX1, DUSP9, ADCY5 and APOC3 polymorphisms and the risk of metabolic syndrome (MetS) in Moroccan patients. The study was applied on 316 unrelated individuals from Morocco, 177 MetS patients and 139 controls. The metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. All subjects were genotyped for the following polymorphisms: rs7612463 (UBE2E2), rs560887 (G6PC2), rs340874 (PROX1), rs5945326 (DUSP9), rs11708067 (ADCY5) and rs5128 (APOC3) using TaqMan allelic discrimination assay and PCR-RFLP...
September 11, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28915626/hdl-cholesterol-concentration-in-pregnant-chinese-han-women-of-late-second-trimester-associated-with-genetic-variants-in-cetp-abca1-apoc3-and-galnt2
#8
Mingxuan Cui, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
OBJECTIVE: To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). METHODS: Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887372/the-apolipoprotein-c-iii-gln38lys-variant-associated-with-human-hypertriglyceridemia-is-a-gain-of-function-mutation
#9
Meenakshi Sundaram, Kaitlin R Curtis, Mohsen Amir Alipour, Nicholas D LeBlond, Kaitlyn D Margison, Rebecca A Yaworski, Robin J Parks, Adam D McIntyre, Robert A Hegele, Morgan D Fullerton, Zemin Yao
Recent cell culture and animal studies have suggested that expression of human apo C-III in the liver has a profound impact on the triacylglycerol (TAG)-rich VLDL1 production under lipid-rich conditions. The apoC-III Gln38Lys variant was identified in subjects of Mexican origin with moderate hypertriglyceridemia. We postulated that Gln38Lys (C3(QK)), being a gain-of-function mutation, promotes hepatic VLDL1 assembly/secretion. To test this hypothesis, we expressed C3(QK) in McA-RH7777 cells and apoc3-null mice to contrast its effect with WT apoC-III (C3(WT))...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28865324/the-impact-of-apoa5-apob-apoc3-and-abca1-gene-polymorphisms-on-ischemic-stroke-evidence-from-a-meta-analysis
#10
Anthony Au, Lyn R Griffiths, Looi Irene, Cheah Wee Kooi, Loo Keat Wei
BACKGROUND AND AIMS: Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk. METHODS: A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017...
August 19, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28853084/gene-gene-interactions-of-apolipoprotein-gene-polymorphic-variants-in-adolescents-with-essential-arterial-hypertension-and-dyslipidemia
#11
O V Kalyuzhnaya, T A Bairova, L I Kolesnikova
Using MDR bioinformatic analysis we studied gene-gene interactions between apolipoprotein genes in adolescents with essential arterial hypertension and dyslipidemia against the background of essential arterial hypertension. Optimal models of gene-gene interactions were formed. The six-locus model was the most significant: (ApoA1(+83T), ApoA1(-75A), ApoB(Del), ApoC3(S2), ApoE(ε2), ApoE(ε4). The maximum synergism in both adolescent groups were shown for allele variants ApoA1(-75A), ApoB(Del), and ApoE(ε4)...
August 29, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28825717/a-human-apoc3-missense-variant-and-monoclonal-antibody-accelerate-apoc-iii-clearance-and-lower-triglyceride-rich-lipoprotein-levels
#12
Sumeet A Khetarpal, Xuemei Zeng, John S Millar, Cecilia Vitali, Amritha Varshini Hanasoge Somasundara, Paolo Zanoni, James A Landro, Nicole Barucci, William J Zavadoski, Zhiyuan Sun, Hans de Haard, Ildikó V Toth, Gina M Peloso, Pradeep Natarajan, Marina Cuchel, Sissel Lund-Katz, Michael C Phillips, Alan R Tall, Sekar Kathiresan, Paul DaSilva-Jardine, Nathan A Yates, Daniel J Rader
Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD...
September 2017: Nature Medicine
https://www.readbyqxmd.com/read/28701354/pleiotropic-effects-of-apolipoprotein-c3-on-hdl-functionality-and-adipose-tissue-metabolic-activity
#13
Evangelia Zvintzou, Marie Lhomme, Stella Chasapi, Serafoula Filou, Vassilis Theodoropoulos, Eva Xapapadaki, Anatol Kontush, George Spyroulias, Constantinos C Tellis, Alexandros D Tselepis, Caterina Constantinou, Kyriakos E Kypreos
APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype...
September 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28694296/apolipoprotein-c-iii-inhibits-triglyceride-hydrolysis-by-gpihbp1-bound-lpl
#14
Mikael Larsson, Christopher M Allan, Rachel S Jung, Patrick J Heizer, Anne P Beigneux, Stephen G Young, Loren G Fong
apoC-III is often assumed to retard the intravascular processing of triglyceride-rich lipoproteins (TRLs) by inhibiting LPL, but that view is based largely on studies of free LPL. We now recognize that intravascular LPL is neither free nor loosely bound, but instead is tightly bound to glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) on endothelial cells. Here, we revisited the effects of apoC-III on LPL, focusing on apoC-III's capacity to affect the activity of GPIHBP1-bound LPL. We found that TRLs from APOC3 transgenic mice bound normally to GPIHBP1-bound LPL on cultured cells in vitro and to heart capillaries in vivo...
September 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28662995/simplifying-the-human-serum-proteome-for-discriminating-patients-with-bipolar-disorder-of-other-psychiatry-conditions
#15
Jemmyson Romário de Jesus, Rodrigo Moretto Galazzi, Tatiani Brenelli de Lima, Cláudio Eduardo Muller Banzato, Luiz Fernando de Almeida Lima E Silva, Clarissa de Rosalmeida Dantas, Fábio Cézar Gozzo, Marco Aurélio Zezzi Arruda
PURPOSE: An exploratory analysis using proteomic strategies in blood serum of patients with bipolar disorder (BD), and with other psychiatric conditions such as Schizophrenia (SCZ), can provide a better understanding of this disorder, as well as their discrimination based on their proteomic profile. METHODS: The proteomic profile of blood serum samples obtained from patients with BD using lithium or other drugs (N=14), healthy controls, including non-family (HCNF; N=3) and family (HCF; N=9), patients with schizophrenia (SCZ; N=23), and patients using lithium for other psychiatric conditions (OD; N=4) were compared...
June 27, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28635360/the-association-between-apolipoprotein-a1-c3-a5-gene-cluster-promoter-polymorphisms-and-risk-of-ischemic-stroke-in-the-northern-chinese-han-population
#16
Yanzhe Wang, Fang Liu, Lei Li, Shumin Deng, Zhiyi He
Objective Given its effects on lipid metabolism, the apolipoprotein A1-C3-A5 ( APOA1-C3-A5) gene cluster is thought to play an important role in ischemic stroke pathogenesis. Here, we evaluated whether the APOA1-C3-A5 cluster is associated with ischemic stroke in the northern Chinese Han population. Methods This case-control study analyzed 812 patients with ischemic stroke and 844 healthy controls with regard to four APOA1-C3-A5 cluster promoter single nucleotide polymorphisms (SNPs), rs670, rs2854116, rs2854117, and rs662799, using the SNaPshot Multiplex sequencing assay...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28610615/quantitative-trait-loci-at-the-11q23-3-chromosomal-region-related-to-dyslipidemia-in-the-population-of-andhra-pradesh-india
#17
Rayabarapu Pranavchand, Battini Mohan Reddy
BACKGROUND: Given the characteristic atherogenic dyslipidemia of south Indian population and crucial role of APOA1, APOC3, APOA4 and APOA5 genes clustered in 11q23.3 chromosomal region in regulating lipoprotein metabolism and cholesterol homeostasis, a large number of recently identified variants are to be explored for their role in regulating the serum lipid parameters among south Indians. METHODS: Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of the 11q23...
June 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28599304/hdl-cholesterol-concentration-in-pregnant-chinese-han-women-of-late-second-trimester-associated-with-genetic-variants-in-cetp-abca1-apoc3-and-galnt2
#18
Mingxuan Cui, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
OBJECTIVE: To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). METHODS: Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595549/apoc-iii-antisense-oligonucleotides-a-new-option-for-the-treatment-of-hypertriglyceridemia
#19
Joel Schmitz, Ioanna Gouni-Berthold
Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28548292/hypertriglyceridemic-acute-pancreatitis-in-emergency-department-typical-clinical-features-and-genetic-variants
#20
Wan Jun Chen, Xiao Fan Sun, Rui Xue Zhang, Min Jie Xu, Tong Hai Dou, Xiao Bin Zhang, Min Zhong, Wei Qiang Yang, Li Liu, Xiao Ye Lu, Chang Qing Zhu
OBJECTIVE: To investigate the clinical characteristics of patients with hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to hypertriglyceridemia in such patients. METHODS: Clinical data from 329 patients with acute pancreatitis (AP) were analyzed. The patients were divided into the HTGAP group, with fasting serum triglyceride (TG) levels ≥500 mg/dL (5.65 mmol/L), and the non-HTGAP (NHTGAP) group. Targeted next-generation sequencing was applied to 11 HTGAP patients to identify the genetic mutations associated with hypertriglyceridemia, including apolipoprotein A-V (APOA5), APOC2, APOC3 and APOE, BLK, LPL, GPIHBP1 and LMF1...
June 2017: Journal of Digestive Diseases
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