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Mala Ganesan, Sheikh Nizamuddin, Shiva Krishna Katkam, Konda Kumaraswami, Uday Kumar Hosad, Limmy Loret Lobo, Vijay Kumar Kutala, Kumarasamy Thangaraj
BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of mortality worldwide. It is a multi-factorial disease and several studies have demonstrated that the genetic factors play a major role in CAD. Although variations in cholesteryl ester transfer protein (CETP) gene are reported to be associated with CAD, this gene has not been studied in South Indian populations. Hence we evaluated the CETP gene variations in CAD patients of South Indian origin. METHODS: We sequenced all the exons, exon-intron boundaries and UTRs of CETP in 323 CAD patients along with 300 ethnically and age matched controls...
2016: PloS One
Yongzhi Chang, Shuxi Zhou, Enqin Li, Wenfeng Zhao, Yanpeng Ji, Xiaoan Wen, Hongbin Sun, Haoliang Yuan
Cholesteryl Ester Transfer Protein (CETP) is an important therapeutic target for the treatment of atherosclerotic cardiovascular disease. Our molecular modeling study revealed that pentacyclic triterpenoid compounds could mimic the protein-ligand interactions of the endogenous ligand cholesteryl ester (CE) by occupying its binding site. Alignment of the docking conformations of oleanolic acid (OA), ursolic acid (UA) and the crystal conformations of known CETP inhibitor Torcetrapib in the active site proposed the applicability of fragment-based drug design (FBDD) approaches in this study...
September 30, 2016: European Journal of Medicinal Chemistry
Jae-Yong Kim, Eun-Young Lee, Jin Kyun Park, Yeong Wook Song, Jae-Ryong Kim, Kyung-Hyun Cho
OBJECTIVE: In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. METHODS: We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). RESULTS: Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC...
2016: PloS One
Christopher D Anderson, Guido J Falcone, Chia-Ling Phuah, Farid Radmanesh, H Bart Brouwers, Thomas W K Battey, Alessandro Biffi, Gina M Peloso, Dajiang J Liu, Alison M Ayres, Joshua N Goldstein, Anand Viswanathan, Steven M Greenberg, Magdy Selim, James F Meschia, Devin L Brown, Bradford B Worrall, Scott L Silliman, David L Tirschwell, Matthew L Flaherty, Peter Kraft, Jeremiasz M Jagiella, Helena Schmidt, Björn M Hansen, Jordi Jimenez-Conde, Eva Giralt-Steinhauer, Roberto Elosua, Elisa Cuadrado-Godia, Carolina Soriano, Koen M van Nieuwenhuizen, Catharina J M Klijn, Kristiina Rannikmae, Neshika Samarasekera, Rustam Al-Shahi Salman, Catherine L Sudlow, Ian J Deary, Andrea Morotti, Alessandro Pezzini, Joanna Pera, Andrzej Urbanik, Alexander Pichler, Christian Enzinger, Bo Norrving, Joan Montaner, Israel Fernandez-Cadenas, Pilar Delgado, Jaume Roquer, Arne Lindgren, Agnieszka Slowik, Reinhold Schmidt, Chelsea S Kidwell, Steven J Kittner, Salina P Waddy, Carl D Langefeld, Goncalo Abecasis, Cristen J Willer, Sekar Kathiresan, Daniel Woo, Jonathan Rosand
OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH...
September 22, 2016: Annals of Neurology
Yukihide Momozawa, Masato Akiyama, Yoichiro Kamatani, Satoshi Arakawa, Miho Yasuda, Shigeo Yoshida, Yuji Oshima, Ryusaburo Mori, Koji Tanaka, Keisuke Mori, Satoshi Inoue, Hiroko Terasaki, Tetsuhiro Yasuma, Shigeru Honda, Akiko Miki, Maiko Inoue, Kimihiko Fujisawa, Kanji Takahashi, Tsutomu Yasukawa, Yasuo Yanagi, Kazuaki Kadonosono, Koh-Hei Sonoda, Tatsuro Ishibashi, Atsushi Takahashi, Michiaki Kubo
AMD is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analyzed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method...
October 3, 2016: Human Molecular Genetics
Julian C van Capelleveen, John J P Kastelein, Aeilko H Zwinderman, Sander J H van Deventer, Heidi L Collins, Steven J Adelman, Patrick Round, John Ford, Daniel J Rader, G Kees Hovingh
BACKGROUND: TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. OBJECTIVE: To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution. METHODS: Total, non-ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215)...
September 2016: Journal of Clinical Lipidology
Belinda A Di Bartolo, MyNgan Duong, Stephen J Nicholls
PURPOSE OF REVIEW: Inhibition of cholesteryl ester transfer protein (CETP) has received considerable interest by virtue of its favorable effects on atherogenic and protective lipid parameters. The impact of CETP inhibitors in large clinical outcome trials will be reviewed. RECENT FINDINGS: Population and genetic studies demonstrate that low CETP activity associates with lower rates of cardiovascular events. Inhibiting CETP activity in animal models has a favorable impact on experimental atherosclerosis...
September 26, 2016: Current Opinion in Lipidology
Martin Ellis, Eilon Krashin, Orly Hamburger-Avnery, Sarah Gan, Avishai Elis, Osnat Ashur-Fabian
Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalization period of bcr-abl, blood counts, and lipids in 40 CML patients, 19 of which co-treated with statins, during short (<12 months) and prolonged (>12 months) imatinib treatment. Prior statins treatment did not hinder nor sensitized imatinib's anti-leukemic and lipid-lowering effects...
September 21, 2016: Leukemia & Lymphoma
Yun-Xia Zhang, Ya Su, Li Tang, Ze-Xing Yang, Dai-Feng Zhou, Yi-Min Qiu, Wang-Wei Cai
OBJECTIVE: In this paper, we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island. METHODS: We tested the TaqIB and I405V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package (Version 19.0). RESULTS: Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P < 0...
September 2016: Asian Pacific Journal of Tropical Medicine
Tain-Junn Cheng, Shu-Wen Lin, Chih-Wei Chen, How-Ran Guo, Ying-Jang Wang
Chronic arsenic exposure is associated with cerebrovascular disease and the formation of atherosclerotic lesions. Our previous study demonstrated that arsenic trioxide (ATO) exposure was associated with atherosclerotic lesion formation through alterations in lipid metabolism in the reverse cholesterol transport process. In mouse livers, the expression of the liver X receptor β (LXR-β) and the cholesteryl ester transfer protein (CETP) was suppressed without any changes to the lipid profile. The aim of this study was to elucidate whether ATO contributes to atherosclerotic lesions by suppressing LXR-β and CETP levels in hepatocytes...
October 25, 2016: Chemico-biological Interactions
Jian Zhu, Meijuan Lu, Lixia Zhu
The human cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to other lipoproteins and has been established as an attractive target for reducing the risk of atherosclerosis. Here, an amphipathic α-helix peptide, namely SBH-peptide ((465)EHLLVDFLQSLS(476)), was derived from the C-terminal tail of CETP. The peptide exhibits self-binding capability towards the CETP. Crystal structure analysis, molecular dynamics (MD) simulations and ab initio electron correlation characterizations of CETP-SBH-peptide complex system revealed that the Phe471 residue plays a key role in SBH-peptide binding, which can form a π-π stacking with the Phe197 residue of CETP...
October 2016: Bioorganic Chemistry
Shu-Xia Guo, Ming-Hong Yao, Yu-Song Ding, Jing-Yu Zhang, Yi-Zhong Yan, Jia-Ming Liu, Mei Zhang, Dong-Sheng Rui, Qiang Niu, Jia He, Heng Guo, Ru-Lin Ma
BACKGROUND: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. METHODS: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians...
2016: International Journal of Environmental Research and Public Health
Dimitrios Agapakis, Christos Savopoulos, Kyriakos E Kypreos, Emma Gbandi, Stavros Iliadis, Apostolos I Hatzitolios, Antonis Goulas
OBJECTIVE: To examine the association of 2 common polymorphisms in high-density lipoprotein (HDL)-related genes, namely, cholesterol ester transfer protein CETP Taq1B (rs708272) and endothelial lipase LIPG Thr111Ile (rs2000813), with glycated hemoglobin (A1C), blood lipid levels and the risk for type 2 diabetes in a group of hyperlipidemic patients from northern Greece. METHODS: We categorized 175 patients with hyperlipidemia into 2 subgroups according to the presence or absence of type 2 diabetes, defined as a recent diagnosis, A1C >6...
August 30, 2016: Canadian Journal of Diabetes
Iris Postmus, Helen R Warren, Stella Trompet, Benoit J Arsenault, Christy L Avery, Joshua C Bis, Daniel I Chasman, Catherine E de Keyser, Harshal A Deshmukh, Daniel S Evans, QiPing Feng, Xiaohui Li, Roelof A J Smit, Albert V Smith, Fangui Sun, Kent D Taylor, Alice M Arnold, Michael R Barnes, Bryan J Barratt, John Betteridge, S Matthijs Boekholdt, Eric Boerwinkle, Brendan M Buckley, Y-D Ida Chen, Anton J M de Craen, Steven R Cummings, Joshua C Denny, Marie Pierre Dubé, Paul N Durrington, Gudny Eiriksdottir, Ian Ford, Xiuqing Guo, Tamara B Harris, Susan R Heckbert, Albert Hofman, G Kees Hovingh, John J P Kastelein, Leonore J Launer, Ching-Ti Liu, Yongmei Liu, Thomas Lumley, Paul M McKeigue, Patricia B Munroe, Andrew Neil, Deborah A Nickerson, Fredrik Nyberg, Eoin O'Brien, Christopher J O'Donnell, Wendy Post, Neil Poulter, Ramachandran S Vasan, Kenneth Rice, Stephen S Rich, Fernando Rivadeneira, Naveed Sattar, Peter Sever, Sue Shaw-Hawkins, Denis C Shields, P Eline Slagboom, Nicholas L Smith, Joshua D Smith, Nona Sotoodehnia, Alice Stanton, David J Stott, Bruno H Stricker, Til Stürmer, André G Uitterlinden, Wei-Qi Wei, Rudi G J Westendorp, Eric A Whitsel, Kerri L Wiggins, Russell A Wilke, Christie M Ballantyne, Helen M Colhoun, L Adrienne Cupples, Oscar H Franco, Vilmundur Gudnason, Graham Hitman, Colin N A Palmer, Bruce M Psaty, Paul M Ridker, Jeanette M Stafford, Charles M Stein, Jean-Claude Tardif, Mark J Caulfield, J Wouter Jukema, Jerome I Rotter, Ronald M Krauss
BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals...
September 1, 2016: Journal of Medical Genetics
Swarup A V Shah, Altaf A Kondkar, Tester F Ashavaid
BACKGROUND: With an increase in the discovery of newer genetic loci/polymorphisms in complex multifactorial diseases, there is also an increased need for methods that can simultaneously genotype multiple loci in a cost-effective manner. Using coronary artery disease (CAD) as a model, the study aimed to develop an in-house multilocus assay for simultaneous detection of 17 genetic variants in 11 genes implicated in CAD. METHODS: A multiplex polymerase chain reaction (PCR)-based reverse line blot hybridization (MPCR-RLBH) approach was used, where each DNA sample was amplified using two separate MPCRs, and the alleles were genotyped using covalently immobilized, amino-linked sequence-specific oligonucleotide probes using an enhanced chemiluminescence system...
November 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Y H Hu, J M Liu, M Zhang, J He, Y Z Yan, J L Ma, R L Ma, H Guo, D S Rui, F Sun, L L Mu, Q Niu, Y S Ding, J Y Zhang, S G Li, S X Guo
OBJECTIVE: To explore the relationship between the polymorphisms and haplotypes in the CETP gene and dyslipidemia among Xinjiang Kazak and Uygur residents. METHODS: A population status survey was performed from 2010 to 2011 in Kashgar Xinjiang Uygur and Kazak residents, stratified cluster sampling method was used to select Uygur, Kazak residents with abnormal blood lipid values (n=367 and 345, respectively) as the dyslipidemia groups, and to select residents with normal lipid values as control group from the same area (n=374 and 390, respectively)...
August 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
Yadong Yu, Yu-Lin Kuang, Dongsheng Lei, Xiaobo Zhai, Meng Zhang, Ronald M Krauss, Gang Ren
Human VLDLs assembled in the liver and secreted into the circulation supply energy to peripheral tissues. VLDL lipolysis yields atherogenic LDLs and VLDL remnants that strongly correlate with CVD. Although the composition of VLDL particles has been well-characterized, their 3D structure is elusive because of their variations in size, heterogeneity in composition, structural flexibility, and mobility in solution. Here, we employed cryo-electron microscopy and individual-particle electron tomography to study the 3D structure of individual VLDL particles (without averaging) at both below and above their lipid phase transition temperatures...
October 2016: Journal of Lipid Research
Toshimi Kido, Hideaki Kurata, Kazuo Kondo, Hiroshige Itakura, Mitsuyo Okazaki, Takeyoshi Urata, Shinji Yokoyama
Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency...
2016: Scientific Reports
Xiangfeng Lu, Jun Li, Huaixing Li, Yang Chen, Laiyuan Wang, Meian He, Yiqin Wang, Liang Sun, Yao Hu, Jianfeng Huang, Feijie Wang, Xuezhen Liu, Shufeng Chen, Kuai Yu, Xueli Yang, Zengnan Mo, Xu Lin, Tangchun Wu, Dongfeng Gu
Previously identified common variants explain only a small fraction of the trait heritability and at most loci the identities of the underlying causal genes and their functional variants still remain unknown. To identify the low-frequency and rare coding variants that influence lipid levels, we conducted a meta-analysis of exome-wide association studies in 14,473 Chinese subjects, followed by a joint analysis with 1000 genomes imputed data from 6,534 samples. We replicated 24 previously reported lipid loci with exome-wide significance (P < 3...
August 11, 2016: Human Molecular Genetics
Julian Hardy McLain, Andrew Jacob Alsterda, Rohit R Arora
The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an important role in the transfer of lipids between plasma lipoproteins. The CETP inhibitors have been widely studied as a pharmacologic therapy to target plasma cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease . Using CETP inhibitors as cholesterol modifiers was based on the genetic research that found correlations between CETP activity and cholesterol levels. Although CETP inhibitors are successful at altering targeted cholesterol markers, recent phase 3 outcome trials have shown limited benefit on cardiovascular outcomes when combined with the current standard of care...
August 10, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
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