Genomes and Genes
Summary: A group of apolipoproteins that can readily exchange among the various classes of lipoproteins (HDL; VLDL; CHYLOMICRONS). After lipolysis of TRIGLYCERIDES on VLDL and chylomicrons, Apo-C proteins are normally transferred to HDL. The subtypes can modulate remnant binding to receptors, LECITHIN CHOLESTEROL ACYLTRANSFERASE, or LIPOPROTEIN LIPASE.
- Dallinga Thie G, Groenendijk M, Blom R, de Bruin T, De Kant E. Genetic heterogeneity in the apolipoprotein C-III promoter and effects of insulin. J Lipid Res. 2001;42:1450-6 pubmed..This means that in vivo apoC-III transcription not only depends upon insulin but appears to be mediated by other mechanisms. ..
- Zhang Q, Liu Y, Liu B, Fan P, Cavanna J, Galton D. Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects. Mol Genet Metab. 1998;64:177-83 pubmed..We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted. ..
- Takahashi T, Hirano T, Okada K, Adachi M. Apolipoprotein CIII deficiency prevents the development of hypertriglyceridemia in streptozotocin-induced diabetic mice. Metabolism. 2003;52:1354-9 pubmed..These results suggest that apo CIII deficiency prevents the development of hypertriglyceridemia associated with diabetes by stimulating TG removal, possibly by promoting the interaction of VLDL with the TG removal system. ..
- Onat A, Hergenc G, Sansoy V, Fobker M, Ceyhan K, Toprak S, et al. Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis. 2003;168:81-9 pubmed..In women, despite being correlated with inflammatory risk markers, the significant association of elevated levels of apoC-III with CHD did not prove to be independent of age. ..
- Russo G, Meigs J, Cupples L, Demissie S, Otvos J, Wilson P, et al. Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study. Atherosclerosis. 2001;158:173-81 pubmed..Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population. ..
- Jong M, Hofker M, Havekes L. Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol. 1999;19:472-84 pubmed
- Tarr P, Taffe P, Bleiber G, Furrer H, Rotger M, Martinez R, et al. Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis. 2005;191:1419-26 pubmed..Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia. ..
- Lai C, Parnell L, Ordovas J. The APOA1/C3/A4/A5 gene cluster, lipid metabolism and cardiovascular disease risk. Curr Opin Lipidol. 2005;16:153-66 pubmed..Therefore, studies focusing on regulatory variants may be more fruitful to locate/define future therapeutic targets. ..
- Wu J, Kao J, Wen M, Lo S. DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: correlation of plasma APOCIII with triglyceride level and body mass index. J Formos Med Assoc. 2000;99:367-74 pubmed
- Chhabra S, Narang R, Lakshmy R, Vasisht S, Agarwal D, Srivastava L, et al. Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD. Mol Cell Biochem. 2004;259:59-66 pubmed..Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD. ..
- Altomonte J, Cong L, Harbaran S, Richter A, Xu J, Meseck M, et al. Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. J Clin Invest. 2004;114:1493-503 pubmed
- Bonnet E, Ruidavets J, Tuech J, Ferrieres J, Collet X, Fauvel J, et al. Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy. J Clin Endocrinol Metab. 2001;86:296-302 pubmed..These results document the accumulation of potentially atherogenic lipoparticles under PIs. Apo C-III may play a pivotal role in the development of hypertriglyceridemia and lipodystrophy. ..
- Olivieri O, Martinelli N, Sandri M, Bassi A, Guarini P, Trabetti E, et al. Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and "insulin-resistant" T-455C APOC3 gene polymorphism in heart disease patients: example of gene-diet interaction. Clin Chem. 2005;51:360-7 pubmed..Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs. ..
- Olivieri O, Bassi A, Stranieri C, Trabetti E, Martinelli N, Pizzolo F, et al. Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. J Lipid Res. 2003;44:2374-81 pubmed..6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents. ..
- Rimland D, Guest J, Hernandez I, Del Rio C, Le N, Brown W. Antiretroviral therapy in HIV-positive men is associated with increased apolipoprotein CIII in triglyceride-rich lipoproteins. HIV Med. 2005;6:326-33 pubmed..These findings, on a background of an older population with additional risk factors of smoking and diabetes, portend future atherosclerotic events in these patients. ..
- Chan D, Watts G, Nguyen M, Barrett P. Apolipoproteins C-III and A-V as predictors of very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics. Arterioscler Thromb Vasc Biol. 2006;26:590-6 pubmed..We also demonstrated that the kinetics of VLDL triglycerides and apoB are closely coupled. Our data do not support a role for plasma apoA-V in regulating VLDL kinetics. ..
- Zeng Q, Dammerman M, Takada Y, Matsunaga A, Breslow J, Sasaki J. An apolipoprotein CIII marker associated with hypertriglyceridemia in Caucasians also confers increased risk in a west Japanese population. Hum Genet. 1995;95:371-5 pubmed..The results suggest that S2-M2 chromosomes carry HTG susceptibility sequences that predate the separation of the Asian and Caucasian races. ..
- Dallinga Thie G, van Linde Sibenius Trip M, Rotter J, Cantor R, Bu X, Lusis A, et al. Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes. J Clin Invest. 1997;99:953-61 pubmed..Therefore, two different susceptibility loci exist in the gene cluster, demonstrating the paradigm of complex genetic contribution to FCH. ..
- Maeda N, Li H, Lee D, Oliver P, Quarfordt S, Osada J. Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. J Biol Chem. 1994;269:23610-6 pubmed..These data indicate that ApoC-III modulates the catabolism of triglyceride-rich lipoproteins and plays a role in the postprandial management of triglycerides. ..
- Ito Y, Azrolan N, O CONNELL A, Walsh A, Breslow J. Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Science. 1990;249:790-3 pubmed..Thus, overexpression of apolipoprotein CIII can be a primary cause of hypertriglyceridemia in vivo and may provide one possible etiology for this common disorder in humans. ..
- Henderson H, Landon S, Michie J, Berger G. Association of a DNA polymorphism in the apolipoprotein C-III gene with diverse hyperlipidaemic phenotypes. Hum Genet. 1987;75:62-5 pubmed..These results suggest that the Sst-1 site is linked to a gene defect with a minor or subtle phenotypic effect which enhances the expression of a co-existent major monogenic defect of lipoprotein transport. ..
- Karathanasis S. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci U S A. 1985;82:6374-8 pubmed..6% identical to rat apoAIV. These results indicate that apoAI, apoCIII, and apoAIV genes are closely linked in the human genome and suggest that all three of them are derived from a common ancestral precursor. ..
- Windler E, Havel R. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J Lipid Res. 1985;26:556-65 pubmed..Preferential loss of apolipoprotein C-II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL. ..
- Hegele R, Breckenridge W, Cox D, Maguire G, Little J, Connelly P. Interaction between variant apolipoproteins C-II and E that affects plasma lipoprotein concentrations. Arterioscler Thromb. 1991;11:1303-9 pubmed
- Birchbauer A, Knipping G, Juritsch B, Aschauer H, Zechner R. Characterization of the apolipoprotein AI and CIII genes in the domestic pig. Genomics. 1993;15:643-52 pubmed..Our studies demonstrate the presence of an apo CIII gene, an apo CIII mRNA, and an apo CIII protein in the pig and, therefore, exclude a hypothesized apo CIII deficiency in these animals. ..
- Morita S, Okuhira K, Tsuchimoto N, Vertut Doï A, Saito H, Nakano M, et al. Effects of sphingomyelin on apolipoprotein E- and lipoprotein lipase-mediated cell uptake of lipid particles. Biochim Biophys Acta. 2003;1631:169-76 pubmed..b>Apolipoproteins C-II and C-III inhibited the apoE-mediated uptake of SM containing emulsions more effectively...
- Fernandez M, Metghalchi S, Vega Lopez S, Conde Knape K, Lohman T, Cordero MacIntyre Z. Beneficial effects of weight loss on plasma apolipoproteins in postmenopausal women. J Nutr Biochem. 2004;15:717-21 pubmed..436) and apo E (r=0.354) over 6 months. These results suggest that weight loss may have multifactorial effects on lipoprotein metabolism, resulting in better plasma lipid and apoprotein profiles. ..
- Pallaud C, Gueguen R, Sass C, Grow M, Cheng S, Siest G, et al. Genetic influences on lipid metabolism trait variability within the Stanislas Cohort. J Lipid Res. 2001;42:1879-90 pubmed..The newly observed relationships between E-selectine gene and lipid concentrations support the hypotheses of multiple metabolic pathways contributing to the complexity of lipids variability. ..
- Wopereis S, Morava E, Grunewald S, Mills P, Winchester B, Clayton P, et al. A combined defect in the biosynthesis of N- and O-glycans in patients with cutis laxa and neurological involvement: the biochemical characteristics. Biochim Biophys Acta. 2005;1741:156-64 pubmed..Improper glycosylation of ECM proteins of skin may form the pathophysiological basis for the cutis laxa phenotype. ..
- Hoffer M, van Eck M, Havekes L, Hofker M, Frants R. The mouse apolipoprotein C1 gene: structure and expression. Genomics. 1993;18:37-42 pubmed..The delineation of the sequence and structural organization of the mouse Apoc1 gene is an essential step in enhancing the use of mouse models to study the function of apoC1 in the lipoprotein metabolism. ..
- Wassef H, Bernier L, Davignon J, Cohn J. Synthesis and secretion of apoC-I and apoE during maturation of human SW872 liposarcoma cells. J Nutr. 2004;134:2935-41 pubmed..Furthermore, apoC-I and apoE production are differentially regulated at the transcriptional level, and long-term treatment with insulin has an inhibitory rather than stimulatory effect on apoC-I and apoE production. ..
- Pullinger C, Zysow B, Hennessy L, Frost P, Malloy M, Kane J. Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia. Hum Mol Genet. 1993;2:69-74 pubmed..The presence of other factors acting together with the variant may predispose to elevated lipid levels. ..
- Morinville V, Perrault J. Genetic disorders of the pancreas. Gastroenterol Clin North Am. 2003;32:763-87 pubmed..All of us may now look forward to the application of this incredible knowledge to the therapeutic solutions so eagerly awaited. ..
- Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas F, Sacks F. Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation. 2006;113:691-700 pubmed..These results indicate that apoCIII not only modulates lipoprotein metabolism but also may directly contribute to the development of atherosclerosis. ..
- Wan Y, Cai Y, Lungo W, Fu P, Locker J, French S, et al. Peroxisome proliferator-activated receptor alpha-mediated pathways are altered in hepatocyte-specific retinoid X receptor alpha-deficient mice. J Biol Chem. 2000;275:28285-90 pubmed..These data suggested that in comparison to PPARalpha, hepatocyte RXRalpha has its unique role in lipid homeostasis and that the effect of RXRalpha, -beta, and -gamma is redundant in certain aspects. ..
- Chan D, Watts G, Barrett P, Mamo J, Redgrave T. Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity. Clin Chem. 2002;48:278-83 pubmed..020). Viscerally obese individuals have insulin resistance and increased plasma concentrations of triglyceride-rich lipoprotein remnants, which may be attributable to decreased catabolism of these particles. ..
- Dallinga Thie G, Berk Planken I, Bootsma A, Jansen H. Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides. Diabetes Care. 2004;27:1358-64 pubmed..These data indicate a potentially important antiatherogenic effect of statin treatment and may explain (part of) the triglyceride-lowering effect of atorvastatin. ..
- Descamps O, Bruniaux M, Guilmot P, Tonglet R, Heller F. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers. Atherosclerosis. 2004;172:287-98 pubmed..It suggests that proteic components of maternal lipoproteins strongly control the metabolism of maternal lipoproteins carried out at the surface of the placenta to assure the cholesterol delivery to the fetus. ..
- Poduslo S, Yin X, Hargis J, Brumback R, Mastrianni J, Schwankhaus J. A familial case of Alzheimer's disease without tau pathology may be linked with chromosome 3 markers. Hum Genet. 1999;105:32-7 pubmed..However, there was linkage with chromosome 3 markers. Thus, this form of Alzheimer's disease with a pathology of plaques only is linked with markers on chromosome 3. ..
- Jong M, van Dijk K, Dahlmans V, van der Boom H, Kobayashi K, Oka K, et al. Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor. Biochem J. 1999;338 ( Pt 2):281-7 pubmed
- Gursky O, Atkinson D. Thermodynamic analysis of human plasma apolipoprotein C-1: high-temperature unfolding and low-temperature oligomer dissociation. Biochemistry. 1998;37:1283-91 pubmed
- Perez Martinez P, Gomez P, Paz E, Marin C, Gavilán Moral E, Lopez Miranda J, et al. Interaction between smoking and the Sstl polymorphism of the apo C-III gene determines plasma lipid response to diet. Nutr Metab Cardiovasc Dis. 2001;11:237-43 pubmed..001). Smoking interacts with the apo CM polymorphism and determines the level of lipid response to dietary changes. ..
- Kaiser J. American Society of Human Genetics meeting. Of worms, mice, and very old men and women. Science. 2004;306:1284 pubmed
- Hiukka A, Fruchart Najib J, Leinonen E, Hilden H, Fruchart J, Taskinen M. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes. Diabetologia. 2005;48:1207-15 pubmed..The elevation of VLDL 1 triglycerides is the major determinant of plasma triglyceride concentration in normal subjects and in type 2 diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2 diabetes. ..
- Hegele R, Connelly P, Hanley A, Sun F, Harris S, Zinman B. Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins. Arterioscler Thromb Vasc Biol. 1997;17:2753-8 pubmed..However, the associations could also have resulted from linkage disequilibrium with other functional variants in APOC3 or the closely linked APOA1 and/or APOA4 genes. ..
- Kim E, Li K, Lieu C, Tong S, Kawai S, Fukutomi T, et al. Expression of apolipoprotein C-IV is regulated by Ku antigen/peroxisome proliferator-activated receptor gamma complex and correlates with liver steatosis. J Hepatol. 2008;49:787-98 pubmed publisher..ApoC-IV overexpression may perturb lipid metabolism leading to lipid accumulation. HCV core protein may modulate ApoC-IV expression through Ku antigen and PPARgamma/RXRalpha complex. ..
- Badiou S, Merle De Boever C, Dupuy A, Baillat V, Cristol J, Reynes J. Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?. Atherosclerosis. 2003;168:107-13 pubmed..Lopinavir/ritonavir-containing regimen accentuates the reduction of LDL size. Since fibrates decrease TG and increase LDL size, they appear as a logical option to manage HAART-induced HTG. ..
- Pham C, Hatters D, Lawrence L, Howlett G. Cross-linking and amyloid formation by N- and C-terminal cysteine derivatives of human apolipoprotein C-II. Biochemistry. 2002;41:14313-22 pubmed..These data suggest that the N- and C-termini of apoC-II are close together in the amyloid fibril such that covalent cross-linking of either the N or C end of apoC-II promotes nucleation and the "seeding" of fibril growth. ..
- Amaral M, Oliveira H, Carneiro E, Delghingaro Augusto V, Vieira E, Berti J, et al. Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice. Horm Metab Res. 2002;34:21-6 pubmed..Nonetheless, an additional elevation of FFA induced by heparin in hypertriglyceridemic mice impaired the ipGTT by reducing insulin secretion. ..
- Singh A, Hsia S, Alaupovic P, Sinha Hikim I, Woodhouse L, Buchanan T, et al. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab. 2002;87:136-43 pubmed..Long-term studies are needed to determine whether T supplementation of older men with low T levels affects atherosclerosis progression. ..
- Heeren J, Beisiegel U. Intracellular metabolism of triglyceride-rich lipoproteins. Curr Opin Lipidol. 2001;12:255-60 pubmed..Current concepts concerning its potential relevance with regard to lipoprotein metabolism and atherosclerosis will also be discussed. ..
- Brzozowska A, Sundvold H, Lien S, Rogne S. Evolutionary conservation of the apolipoprotein E-C1-C2 gene cluster on bovine chromosome 18q24. Gene. 2000;241:241-5 pubmed..By means of cosmid mapping, we further demonstrate that the APOE-APOC1-APOC2 gene cluster is evolutionary conserved in cattle. ..
- Islam M, Raitakari O, Juonala M, Kahonen M, Hutri Kähönen N, Collings A, et al. Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms and their association with carotid artery intima-media thickness in the Finnish population. The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2005;180:79-86 pubmed..However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups (p<0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns. ..