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Cholesterol, Genetics, and Medications

Due to space limitations, the abbreviations table and references for this article have been published online. 

References

1.     D’Agostino RB, Vasan RS, Pencina MJ, et al. General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study. Circulation. 2008;117(6):743-753.
2.     Sniderman AD, Williams K, Contois JH, et al. A Meta-Analysis of Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, and Apolipoprotein B as Markers of Cardiovascular Risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337-345.
3.     Genser B, März W. Low density lipoprotein cholesterol, statins and cardiovascular events: a meta-analysis. Clin Res Cardiol Off J Ger Card Soc. 2006;95(8):393-404.
4.     Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934.
5.     Herttua K, Martikainen P, Batty GD, Kivimäki M. Poor Adherence to Statin and Antihypertensive Therapies as Risk Factors for Fatal Stroke. J Am Coll Cardiol. 2016;67(13):1507-1515.
6.     Roth EM, McKenney JM, Kelly MT, et al. Efficacy and safety of rosuvastatin and fenofibric acid combination therapy versus simvastatin monotherapy in patients with hypercholesterolemia and hypertriglyceridemia: a randomized, double-blind study. Am J Cardiovasc Drugs Drugs Devices Interv. 2010;10(3):175-186.
7.     Gelissen IC, McLachlan AJ. The pharmacogenomics of statins. Pharmacol Res. 2014;88:99-106.
8.     Abifadel M, Varret M, Rabès J-P, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154-156. doi:10.1038/ng1161.
9.     Wang L-J, Song B-L. Niemann-Pick C1-Like 1 and cholesterol uptake. Biochim Biophys Acta. 2012;1821(7):964-972.
10.     Yu L. The structure and function of Niemann-Pick C1-like 1 protein. Curr Opin Lipidol. 2008;19(3):263-269.
11.     Phan BAP, Dayspring TD, Toth PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415-427.
12.     Khaitlina SY. Intracellular transport based on actin polymerization. Biochem Mosc. 2014;79(9):917-927.
13.     Hao M, Lin SX, Karylowski OJ, Wustner D, McGraw TE, Maxfield FR. Vesicular and Non-vesicular Sterol Transport in Living Cells: THE ENDOCYTIC RECYCLING COMPARTMENT IS A MAJOR STEROL STORAGE ORGANELLE. J Biol Chem. 2002;277(1):609-617.
14.     Nguyen TM, Sawyer JK, Kelley KL, Davis MA, Rudel LL. Cholesterol esterification by ACAT2 is essential for efficient intestinal cholesterol absorption: evidence from thoracic lymph duct cannulation. J Lipid Res. 2012;53(1):95-104.
15.     Wüstner D, Solanko K. How cholesterol interacts with proteins and lipids during its intracellular transport. Biochim Biophys Acta. 2015;1848(9):1908-1926.
16.     Du X, Kumar J, Ferguson C, et al. A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol trafficking. J Cell Biol. 2011;192(1):121-135.
17.     Iqbal J, Hussain MM. Intestinal lipid absorption. Am J Physiol Endocrinol Metab. 2009;296(6):E1183-1194.
18.     Mansbach CM, Gorelick F. Development and physiological regulation of intestinal lipid absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons. Am J Physiol Gastrointest Liver Physiol. 2007;293(4):G645-650.
19.     Giammanco A, Cefalù AB, Noto D, Averna MR. The pathophysiology of intestinal lipoprotein production. Front Physiol. 2015;6:61.
20.     Xiao C, Lewis GF. Regulation of chylomicron production in humans. Biochim Biophys Acta. 2012;1821(5):736-746.
21.     Black DD. Development and Physiological Regulation of Intestinal Lipid Absorption. I. Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion. AJP Gastrointest Liver Physiol. 2007;293(3):G519-G524.
22.     Randolph GJ, Miller NE. Lymphatic transport of high-density lipoproteins and chylomicrons. J Clin Invest. 2014;124(3):929-935.
23.     Huang L-H, Elvington A, Randolph GJ. The role of the lymphatic system in cholesterol transport. Front Pharmacol. 2015;6.
24.     Ramasamy I. Recent advances in physiological lipoprotein metabolism. Clin Chem Lab Med CCLM. 2014;52(12).
25.     Li Y, He P-P, Zhang D-W, et al. Lipoprotein lipase: from gene to atherosclerosis. Atherosclerosis. 2014;237(2):597-608.
26.     Péterfy M. Lipase maturation factor 1: A lipase chaperone involved in lipid metabolism. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2012;1821(5):790-794.
27.     Beigneux AP, Davies BSJ, Gin P, et al. Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons. Cell Metab. 2007;5(4):279-291.
28.     Adeyo O, Goulbourne CN, Bensadoun A, Beigneux AP, Fong LG, Young SG. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins. J Intern Med. 2012;272(6):528-540.
29.     Sacks FM. The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia: Curr Opin Lipidol. 2015;26(1):56-63.
30.     Martins IJ, Hone E, Chi C, Seydel U, Martins RN, Redgrave TG. Relative roles of LDLr and LRP in the metabolism of chylomicron remnants in genetically manipulated mice. J Lipid Res. 2000;41(2):205-213.
31.     Pfeffer S, Burbaum L, Unverdorben P, et al. Structure of the native Sec61 protein-conducting channel. Nat Commun. 2015;6:8403.
32.     Fisher EA, Pan M, Chen X, et al. The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways. J Biol Chem. 2001;276(30):27855-27863.
33.     Goldstein JL, DeBose-Boyd RA, Brown MS. Protein Sensors for Membrane Sterols. Cell. 2006;124(1):35-46.
34.     Irisawa M, Inoue J, Ozawa N, Mori K, Sato R. The Sterol-sensing Endoplasmic Reticulum (ER) Membrane Protein TRC8 Hampers ER to Golgi Transport of Sterol Regulatory Element-binding Protein-2 (SREBP-2)/SREBP Cleavage-activated Protein and Reduces SREBP-2 Cleavage. J Biol Chem. 2009;284(42):28995-29004.
35.     Martin S, Parton RG. Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol. 2006;7(5):373-378.
36.     Thiam AR, Forêt L. The physics of lipid droplet nucleation, growth and budding. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2016;1861(8):715-722.
37.     Kory N, Farese RV, Walther TC. Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets. Trends Cell Biol. March 2016.
38.     Kraemer FB, Khor VK, Shen W-J, Azhar S. Cholesterol ester droplets and steroidogenesis. Mol Cell Endocrinol. 2013;371(1-2):15-19.
39.     Sztalryd C, Kimmel AR. Perilipins: Lipid droplet coat proteins adapted for tissue-specific energy storage and utilization, and lipid cytoprotection. Biochimie. 2014;96:96-101.
40.     Olivecrona G. Role of lipoprotein lipase in lipid metabolism. Curr Opin Lipidol. 2016;27(3):233-241.
41.     Mishra SK, Keyel PA, Edeling MA, Dupin AL, Owen DJ, Traub LM. Functional Dissection of an AP-2 2 Appendage-binding Sequence within the Autosomal Recessive Hypercholesterolemia Protein. J Biol Chem. 2005;280(19):19270-19280.
42.     Fuchs C, Traussnigg S, Trauner M. Nuclear Receptor Modulation for the Treatment of Nonalcoholic Fatty Liver Disease. Semin Liver Dis. 2016;36(1):069-086.
43.     Zelcer N, Hong C, Boyadjian R, Tontonoz P. LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor. Science. 2009;325(5936):100-104.
44.     Alrefai WA, Annaba F, Sarwar Z, et al. Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Am J Physiol Gastrointest Liver Physiol. 2007;292(1):G369-376.
45.     Jeong HJ, Lee H-S, Kim K-S, Kim Y-K, Yoon D, Park SW. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res. 2008;49(2):399-409.
46.     Gogonea V. Structural Insights into High Density Lipoprotein: Old Models and New Facts. Front Pharmacol. 2016;6.
47.     Yu X-H, Jiang N, Yao P-B, Zheng X-L, Cayabyab FS, Tang C-K. NPC1, intracellular cholesterol trafficking and atherosclerosis. Clin Chim Acta. 2014;429:69-75.
48.     Pfisterer SG, Peränen J, Ikonen E. LDL–cholesterol transport to the endoplasmic reticulum: current concepts. Curr Opin Lipidol. 2016;27(3):282-287.
49.     Chang T-Y, Li B-L, Chang CCY, Urano Y. Acyl-coenzyme A:cholesterol acyltransferases. AJP Endocrinol Metab. 2009;297(1):E1-E9.
50.     Wang N, Silver DL, Costet P, Tall AR. Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1. J Biol Chem. 2000;275(42):33053-33058.
51.     Kielar D, Dietmaier W, Langmann T, et al. Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real-time reverse transcription-PCR. Clin Chem. 2001;47(12):2089-2097.
52.     Rohatgi A. High-Density Lipoprotein Function Measurement in Human Studies: Focus on Cholesterol Efflux Capacity. Prog Cardiovasc Dis. 2015;58(1):32-40.
53.     Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem. 2000;275(36):28240-28245.
54.     Wang N, Chen W, Linsel-Nitschke P, et al. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest. 2003;111(1):99-107.
55.     An S, Jang Y-S, Park J-S, Kwon B-M, Paik Y-K, Jeong T-S. Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes. Exp Mol Med. 2008;40(4):407.
56.     Rached FH, Chapman MJ, Kontush A. HDL particle subpopulations: Focus on biological function: HDL Particle Subpopulations. BioFactors. 2015;41(2):67-77.
57.     Albers JJ, Vuletic S, Cheung MC. Role of plasma phospholipid transfer protein in lipid and lipoprotein metabolism. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2012;1821(3):345-357.
58.     Norata GD, Tsimikas S, Pirillo A, Catapano AL. Apolipoprotein C-III: From Pathophysiology to Pharmacology. Trends Pharmacol Sci. 2015;36(10):675-687.
59.     Wellington CL, Frikke-Schmidt R. Relation between plasma and brain lipids: Curr Opin Lipidol. 2016;27(3):225-232.
60.     Vitali C, Wellington CL, Calabresi L. HDL and cholesterol handling in the brain. Cardiovasc Res. 2014;103(3):405-413.
61.     Siegel GJ, ed. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6. ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 1999.
62.     Saher G, Stumpf SK. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2015;1851(8):1083-1094.
63.     Mahley RW. Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism. Arterioscler Thromb Vasc Biol. May 2016:ATVBAHA.116.307023
64.     Burlot M-A, Braudeau J, Michaelsen-Preusse K, et al. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology. Hum Mol Genet. 2015;24(21):5965-5976.
65.     Djelti F, Braudeau J, Hudry E, et al. CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer’s disease. Brain. 2015;138(8):2383-2398.
66.     Yvan-Charvet L, Pagler T, Gautier EL, et al. ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation. Science. 2010;328(5986):1689-1693.
67.     Schaftenaar F, Frodermann V, Kuiper J, Lutgens E. Atherosclerosis: the interplay between lipids and immune cells. Curr Opin Lipidol. 2016;27(3):209-215.
68.     Westerterp M, Bochem AE, Yvan-Charvet L, Murphy AJ, Wang N, Tall AR. ATP-Binding Cassette Transporters, Atherosclerosis, and Inflammation. Circ Res. 2014;114(1):157-170.
69.     Di Pietro N, Formoso G, Pandolfi A. Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis. Vascul Pharmacol. May 2016.
70.     Chen B, Li J, Zhu H. AMP-activated protein kinase attenuates oxLDL uptake in macrophages through PP2A/NF-κB/LOX-1 pathway. Vascul Pharmacol. August 2015.
71.     Laguna-Fernández A, Novella S, Bueno-Betí C, Marrugat J, Hermenegildo C. Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak–Stat pathway. Vascul Pharmacol. 2015;73:104-114.
72.     Alaarg A, Zheng KH, van der Valk FM, et al. Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques. Vascul Pharmacol. 2016;82:51-59.
73.     Zhang J, He K, Cai L, et al. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. Chem Biol Interact. March 2016.
74.     Slizgi JR, Lu Y, Brouwer KR, et al. Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury? Toxicol Sci. 2016;149(1):237-250.
75.     Dawson PA, Karpen SJ. Intestinal transport and metabolism of bile acids. J Lipid Res. 2015;56(6):1085-1099.
76.     Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284(5418):1362-1365.
77.     Parks DJ, Blanchard SG, Bledsoe RK, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284(5418):1365-1368.
78.     Ferrebee CB, Dawson PA. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids. Acta Pharm Sin B. 2015;5(2):129-134.
79.     Schonewille M, de Boer JF, Groen AK. Bile salts in control of lipid metabolism: Curr Opin Lipidol. 2016;27(3):295-301.
80.     Chiang JYL. Bile acids: regulation of synthesis. J Lipid Res. 2009;50(10):1955-1966.
81.     Ding L, Yang L, Wang Z, Huang W. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B. 2015;5(2):135-144.
82.     Cicione C, Degirolamo C, Moschetta A. Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver. Hepatol Baltim Md. 2012;56(6):2404-2411.
83.     Kliewer SA, Mangelsdorf DJ. Bile Acids as Hormones: The FXR-FGF15/19 Pathway. Dig Dis. 2015;33(3):327-331.
84.     Zhang F, Yu L, Lin X, et al. Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases. Mol Endocrinol. 2015;29(10):1400-1413.
85.     Nies VJM, Sancar G, Liu W, et al. Fibroblast Growth Factor Signaling in Metabolic Regulation. Front Endocrinol. 2016;6.
86.     Markan KR, Potthoff MJ. Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis. Semin Cell Dev Biol. 2016;53:85-93.
87.     Vítek L, Haluzík M. The role of bile acids in metabolic regulation. J Endocrinol. 2016;228(3):R85-R96.
88.     Choi M, Moschetta A, Bookout AL, et al. Identification of a hormonal basis for gallbladder filling. Nat Med. 2006;12(11):1253-1255.
89.     Zhang J, Li Y. Therapeutic uses of FGFs. Semin Cell Dev Biol. 2016;53:144-154.
90.     Dussault I, Yoo H-D, Lin M, et al. Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance. Proc Natl Acad Sci. 2003;100(3):833-838.
91.     Ridlon JM, Kang D-J, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 2006;47(2):241-259. doi:10.1194/jlr.R500013-JLR200.
92.     Sayin SI, Wahlström A, Felin J, et al. Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-beta-muricholic Acid, a Naturally Occurring FXR Antagonist. Cell Metab. 2013;17(2):225-235.
93.     Miyata, Masaaki. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter protein. Biol Pharm Bull. 2015;38(3):493-496.
94.     Neves AL, Chilloux J, Sarafian MH, Rahim MBA, Boulangé CL, Dumas M-E. The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases. Curr Opin Pharmacol. 2015;25:36-44.
95.     Ridlon JM, Bajaj JS. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics. Acta Pharm Sin B. 2015;5(2):99-105.
96.     Kuribayashi H, Miyata M, Yamakawa H, Yoshinari K, Yamazoe Y. Enterobacteria-mediated deconjugation of taurocholic acid enhances ileal farnesoid X receptor signaling. Eur J Pharmacol. 2012;697(1-3):132-138.
97.     Allayee H, Hazen SL. Contribution of Gut Bacteria to Lipid Levels: Figure.: Another Metabolic Role for Microbes? Circ Res. 2015;117(9):750-754.
98.     Fu J, Bonder MJ, Cenit MC, et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood LipidsNovelty and Significance. Circ Res. 2015;117(9):817-824.
99.     Miyata M, Yamakawa H, Hayashi K, Kuribayashi H, Yamazoe Y, Yoshinari K. Ileal apical sodium-dependent bile acid transporter protein levels are down-regulated through ubiquitin-dependent protein degradation induced by bile acids. Eur J Pharmacol. 2013;714(1-3):507-514.
100.     Ghazalpour A, Cespedes I, Bennett BJ, Allayee H. Expanding role of gut microbiota in lipid metabolism: Curr Opin Lipidol. 2016;27(2):141-147.
101.     Wang Z, Koonen D, Hofker M, Fu J. Gut microbiome and lipid metabolism: from associations to mechanisms. Curr Opin Lipidol. 2016;27(3):216-224.
102.     Teske KA, Bogart JW, Sanchez LM, et al. Synthesis and evaluation of vitamin D receptor-mediated activities of cholesterol and vitamin D metabolites. Eur J Med Chem. 2016;109:238-246.
103.     Tachibana S, Yoshinari K, Chikada T, Toriyabe T, Nagata K, Yamazoe Y. Involvement of Vitamin D receptor in the intestinal induction of human ABCB1. Drug Metab Dispos Biol Fate Chem. 2009;37(8):1604-1610.
104.     Brighton CA, Rievaj J, Kuhre RE, et al. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors. Endocrinology. 2015;156(11):3961-3970.
105.     Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860-921.
106.     Gaudet D. Novel therapies for severe dyslipidemia originating from human genetics. Curr Opin Lipidol. 2016;27(2):112-124.
107.     Goldstein JL, Brown MS. The LDL receptor locus and the genetics of familial hypercholesterolemia. Annu Rev Genet. 1979;13:259-289.
108.     Fredrickson DS. An International Classification of Hyperlipidemias and Hyperlipoproteinemias. Ann Intern Med. 1971;75(3):471.
109.     Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-3490a.
110.     Brautbar A, Leary E, Rasmussen K, Wilson DP, Steiner RD, Virani S. Genetics of familial hypercholesterolemia. Curr Atheroscler Rep. 2015;17(4):491.
111.     Borén J, Ekström U, Agren B, Nilsson-Ehle P, Innerarity TL. The molecular mechanism for the genetic disorder familial defective apolipoprotein B100. J Biol Chem. 2001;276(12):9214-9218.
112.     Levy E. Insights from human congenital disorders of intestinal lipid metabolism. J Lipid Res. 2015;56(5):945-962.
113.     Lange LA, Hu Y, Zhang H, et al. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol. Am J Hum Genet. 2014;94(2):233-245.
114.     Ramasamy I. Update on the molecular biology of dyslipidemias. Clin Chim Acta. 2016;454:143-185.
115.     Appadurai V, DeBarber A, Chiang P-W, et al. Apparent underdiagnosis of Cerebrotendinous Xanthomatosis revealed by analysis of ~60,000 human exomes. Mol Genet Metab. 2015;116(4):298-304.
116.     Björkhem I. Cerebrotendinous xanthomatosis: Curr Opin Lipidol. 2013;24(4):283-287.
117.     Fouchier SW, Defesche JC. Lysosomal acid lipase A and the hypercholesterolaemic phenotype: Curr Opin Lipidol. 2013;24(4):332-338.
118.     Rader DJ. Lysosomal Acid Lipase Deficiency — A New Therapy for a Genetic Lipid Disease. N Engl J Med. 2015;373(11):1071-1073.
119.     Reiner Ž, Guardamagna O, Nair D, et al. Lysosomal acid lipase deficiency – An under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis. 2014;235(1):21-30.
120.     Kidambi S, Patel SB. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. J Clin Pathol. 2008;61(5):588-594.
121.     Buch S, Schafmayer C, Völzke H, et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet. 2007;39(8):995-999.
122.     Andrés D. Klein. The Unique Case of The Niemann-Pick Type C Cholesterol Storage Disorder. Pediatr Endocrinol Rev. 2014;12 (Suppl 1):166-175.
123.     Papandreou A, Gissen P. Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Ther Adv Neurol Disord. 2016;9(3):216-229.
124.     Alejandro Santos-Lazano. Niemann-Pick disease treatment: a systematic review of clinical trials. Ann Transl Med. 2015;3(22):360-369.
125.     Timmins JM, Lee J-Y, Boudyguina E, et al. Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest. 2005;115(5):1333-1342.
126.     Bielicki JK. ABCA1 agonist peptides for the treatment of disease: Curr Opin Lipidol. 2016;27(1):40-46.
127.     Oldoni F, Sinke RJ, Kuivenhoven JA. Mendelian Disorders of High-Density Lipoprotein Metabolism. Circ Res. 2014;114(1):124-142.
128.     Soroka CJ, Boyer JL. Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations. Mol Aspects Med. 2014;37:3-14.
129.     Kubitz R, Dröge C, Stindt J, Weissenberger K, Häussinger D. The bile salt export pump (BSEP) in health and disease. Clin Res Hepatol Gastroenterol. 2012;36(6):536-553.
130.     Zhang Y, Li F, Wang Y, et al. Maternal bile acid transporter deficiency promotes neonatal demise. Nat Commun. 2015;6:8186.
131.     Carmen Lang, Yvonne Meier. Mutations and polymorphisms in the bile salt export pump and the mutidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogentics Genomics. 2007;17:47-60.
132.     Pullinger CR, Eng C, Salen G, et al. Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest. 2002;110(1):109-117.
133.     Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466(7307):707-713.
134.     Di Filippo M, Moulin P, Roy P, et al. Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. J Hepatol. 2014;61(4):891-902.
135.     Hsiao P-J, Lee M-Y, Wang Y-T, et al. MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study. BMC Med Genet. 2015;16(1).
136.     Li X-L, Sui J-Q, Lu L-L, et al. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review. Lipids Health Dis. 2016;15(1).
137.     Gomez-Ospina N, Potter CJ, Xiao R, et al. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun. 2016;7:10713.
138.     van Mil SWC, Milona A, Dixon PH, et al. Functional Variants of the Central Bile Acid Sensor FXR Identified in Intrahepatic Cholestasis of Pregnancy. Gastroenterology. 2007;133(2):507-516.
139.     Seppo Heinonen, Pertti Kirknen. Pregnancy outcome with intrahepatic cholestasis. Obstet Gynecol. 1999;94:189-193.
140.     Cohen JC, Pertsemlidis A, Fahmi S, et al. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci. 2006;103(6):1810-1815.
141.     Polisecki E, Peter I, Simon JS, et al. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. J Lipid Res. 2010;51(5):1201-1207.
142.     Robert A. Hegele, Justin Guy. NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe. Lipids Health Dis. 2005;4:1-5.
143.     Smith CE, Ordovás JM. Update on perilipin polymorphisms and obesity. Nutr Rev. 2012;70(10):611-621.
144.     Sheetal Gandotra. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. 2011;364:740-748.
145.     Carr RM, Ahima RS. Pathophysiology of lipid droplet proteins in liver diseases. Exp Cell Res. 2016;340(2):187-192.
146.     Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci. 2016;130(12):943-986.
147.     Chen J-H, Hsieh C-J, Huang Y-L, et al. Genetic polymorphisms of lipid metabolism gene SAR1 homolog B and the risk of Alzheimer’s disease and vascular dementia. J Formos Med Assoc. 2016;115(1):38-44.
148.     Musso G, Bo S, Cassader M, De Michieli F, Gambino R. Impact of sterol regulatory element-binding factor-1c polymorphism on incidence of nonalcoholic fatty liver disease and on the severity of liver disease and of glucose and lipid dysmetabolism. Am J Clin Nutr. 2013;98(4):895-906.
149.     Ward A, Crean S, Mercaldi CJ, et al. Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2012;38(1):1-17.
150.     Rhinn H, Fujita R, Qiang L, Cheng R, Lee JH, Abeliovich A. Integrative genomics identifies APOE ε4 effectors in Alzheimer’s disease. Nature. 2013;500(7460):45-50.
151.     Stukas S, Robert J, Wellington CL. High-Density Lipoproteins and Cerebrovascular Integrity in Alzheimer’s Disease. Cell Metab. 2014;19(4):574-591.
152.     Lambert J-C, Ibrahim-Verbaas CA, Harold D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452-1458.
153.     Marais D. Dysbetalipoproteinemia: an extreme disorder of remnant metabolism. Curr Opin Lipidol. 2015;26(4):292-297.
154.     Ramsey LB, Johnson SG, Caudle KE, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update. Clin Pharmacol Ther. 2014;96(4):423-428.
155.     Marbach JA, McKeon JL, Ross JL, Duffy D. Novel Treatments for Familial Hypercholesterolemia: Pharmacogenetics at Work. Pharmacother J Hum Pharmacol Drug Ther. 2014;34(9):961-972.
156.     Blom DJ, Fayad ZA, Kastelein JJP, et al. LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design. J Clin Lipidol. 2016;10(2):273-282.
157.     Cuchel M, Rader DJ. Microsomal transfer protein inhibition in humans: Curr Opin Lipidol. 2013;24(3):246-250.
158.     Roeters van Lennep J, Averna M, Alonso R. Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide. J Clin Lipidol. 2015;9(4):607-617.
159.     Marina Cuchel, LeAnne T. Bloeden, et al. Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia. N Engl J Med. 2007;356:148-156.
160.     Samaha FF, McKenney J, Bloedon LT, Sasiela WJ, Rader DJ. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2008;5(8):497-505.
161.     Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. The Lancet. 2013;381(9860):40-46.
162.     Davis KA, Miyares MA. Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Am J Health Syst Pharm. 2014;71(12):1001-1008.
163.     Dixon DL, Sisson EM, Butler M, Higbea A, Muoio B, Turner B. Lomitapide and Mipomersen: Novel Lipid-Lowering Agents for the Management of Familial Hypercholesterolemia. J Cardiovasc Nurs. 2014;29(5):E7-E12.
164.     Kolovou G, Vasiliadis I, Gontoras N, Kolovou V, Hatzigeorgiou G. Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance. Cardiovasc Ther. 2015;33(2):71-78.
165.     Vuorio A, Tikkanen MJ, Kovanen P. Inhibition of hepatic microsomal triglyceride transfer protein – a novel therapeutic option for treatment of homozygous familial hypercholesterolemia. Vasc Health Risk Manag. May 2014:263.
166.     Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2012;33(9):1142-1149.
167.     Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. The Lancet. 2010;375(9719):998-1006.
168.     Panta R, Dahal K, Kunwar S. Efficacy and safety of mipomersen in treatment of dyslipidemia: A meta-analysis of randomized controlled trials. J Clin Lipidol. 2015;9(2):217-225.
169.     Raal FJ, Stein EA. The Effects of Mipomersen on Inhibiting Hepatic VLDL Apolipoprotein B100 Synthesis and Propensity for Hepatic Steatosis. Clin Chem. May 2016.
170.     Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015;36(9):566-575.
171.     Ho PP, Steinman L. Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis. Proc Natl Acad Sci. 2016;113(6):1600-1605.
172.     Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. The Lancet. 2015;385(9972):956-965.
173.     Rinella ME. Nonalcoholic Fatty Liver Disease: A Systematic Review. JAMA. 2015;313(22):2263.
174.     Hirschfield GM, Gershwin ME. The Immunobiology and Pathophysiology of Primary Biliary Cirrhosis. Annu Rev Pathol Mech Dis. 2013;8(1):303-330.
175.     Hirschfield GM, Mason A, Luketic V, et al. Efficacy of Obeticholic Acid in Patients With Primary Biliary Cirrhosis and Inadequate Response to Ursodeoxycholic Acid. Gastroenterology. 2015;148(4):751-761.e8.
176.     Burton BK, Balwani M, Feillet F, et al. A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. N Engl J Med. 2015;373(11):1010-1020.
177.     Balwani M, Breen C, Enns GM, et al. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients With cholesteryl ester storage disease. Hepatology. 2013;58(3):950-957.
178.     Gaudet D, Alexander VJ, Baker BF, et al. Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. N Engl J Med. 2015;373(5):438-447.
179.     Yang X, Lee S-R, Choi Y-S, et al. Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. J Lipid Res. 2016;57(4):706-713.
180.     Digenio A, Dunbar RL, Alexander VJ, et al. Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes. Diabetes Care. June 2016:dc160126.
181.     Barter PJ, Caulfield M, Eriksson M, et al. Effects of Torcetrapib in Patients at High Risk for Coronary Events. N Engl J Med. 2007;357(21):2109-2122.
182.     Kosmas C, DeJesus E, Rosario D, Vittorio T. CETP Inhibition: Past Failures and Future Hopes. Clin Med Insights Cardiol. March 2016:37.
183.     Cannon CP, Shah S, Dansky HM, et al. Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease. N Engl J Med. 2010;363(25):2406-2415.
184.     Schwartz GG, Olsson AG, Abt M, et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med. 2012;367(22):2089-2099.
185.     Arai H, Teramoto T, Daida H, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2016;249:215-223.
186.     Scott LJ. Alipogene Tiparvovec: A Review of Its Use in Adults with Familial Lipoprotein Lipase Deficiency. Drugs. 2015;75(2):175-182.
187.     Gencer B, Lambert G, Mach F. PCSK9 inhibitors. Swiss Med Wkly. April 2015.
188.     Stein EA. What role will proprotein convertase subtilisin/kexin type 9 inhibitors play in hyperlipidemia management?: Curr Opin Endocrinol Diabetes Obes. 2016;23(2):97-105.
189.     Cicero A, Colletti A, Borghi C. Profile of evolocumab and its potential in the treatment of hyperlipidemia. Drug Des Devel Ther. June 2015:3073.
190.     Sahebkar A, Simental-Mendía LE, Guerrero-Romero F, Golledge J, Watts GF. Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta-analysis of clinical trials. Diabetes Obes Metab. 2015;17(11):1042-1055.
191.     Zhang X-L, Zhu Q-Q, Zhu L, et al. Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials. BMC Med. 2015;13(1).
192.     Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol. N Engl J Med. 2012;366(12):1108-1118.
193.     Hypercholesterolemia, low density lipoprotein receptor andproprotein convertase subtilisin/kexin-type 9. J Biomed Res. 2015;29(5).
194.     White CM. Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies Evolocumab and Alirocumab. Ann Pharmacother. 2015;49(12):1327-1335.
195.     Okere AN, Serra C. Evaluation of the Potential Role of Alirocumab in the Management of Hypercholesterolemia in Patients with High-Risk Cardiovascular Disease. Pharmacother J Hum Pharmacol Drug Ther. 2015;35(8):771-779.
196.     McKenney JM. Understanding PCSK9 and anti-PCSK9 therapies. J Clin Lipidol. 2015;9(2):170-186.
197.     Rodriguez F, Knowles JW. PCSK9 Inhibition: Current Concepts and Lessons from Human Genetics. Curr Atheroscler Rep. 2015;17(3).
198.     Li C, Lin L, Zhang W, et al. Efficiency and Safety of Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody on Hypercholesterolemia: A Meta-Analysis of 20 Randomized Controlled Trials. J Am Heart Assoc. 2015;4(6):e001937-e001937.
199.     Lipinski MJ, Benedetto U, Escarcega RO, et al. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016;37(6):536-545.
200.     Shimada YJ, Cannon CP. PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future. Eur Heart J. 2015;36(36):2415-2424.
201.     Gouni-Berthold I, Berthold H. PCSK9 Antibodies for the Treatment of Hypercholesterolemia. Nutrients. 2014;6(12):5517-5533.
202.     Joseph L, Robinson JG. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition and the Future of Lipid Lowering Therapy. Prog Cardiovasc Dis. 2015;58(1):19-31.
203.     Denegri A, Petrova-Slater I, Pasotti E, et al. PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy. J Cardiovasc Med. 2016;17(4):237-244.
204.     Kohan AB, Wang F, Lo C-M, Liu M, Tso P. ApoA-IV: current and emerging roles in intestinal lipid metabolism, glucose homeostasis, and satiety. Am J Physiol - Gastrointest Liver Physiol. 2015;308(6):G472-G481.
205.     Wang F, Kohan AB, Lo C-M, Liu M, Howles P, Tso P. Apolipoprotein A-IV: a protein intimately involved in metabolism. J Lipid Res. 2015;56(8):1403-1418.
206.     Nilsson SK, Lookene A, Beckstead JA, Gliemann J, Ryan RO, Olivecrona G. Apolipoprotein A-V Interaction with Members of the Low Density Lipoprotein Receptor Gene Family †. Biochemistry (Mosc). 2007;46(12):3896-3904.
207.     Shachter, Neil S. Apolipoproteins C-I and C-III as important modulators of lipoprotein metabolism. Curr Opin Lipidol. 2001;12:297-304.
208.    Rabbani B, et al. The promise of whole exome sequencing. J Hum Gen 2014;5-15.

209.    Yang Y, et al. Clinical whole-exome sequenvcing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502-11.

Table of Abbreviations

  • ABCATP-binding cassette
  • ABCA1ATP-binding cassette sub-family A member 1
  • ABCA11bile salt export pump protein gene
  • ABCB1 ATP-binding cassette sub-family B member 1, or p-glycoprotein
  • ABCG1ATP-binding cassette sub-family G member 1
  • ABCG4ATP-binding cassette sub-family G member 4
  • ABCG5ATP-binding cassette sub-family G member 5
  • ABCG8ATP-binding cassette sub-family G member 8
  • Aposee table 2 for apolipoprotein abbreviations
  • ACATsterol O-acyltransferase
  • AP-2 AP-2 complex subunit alpha-1
  • BSEPbile salt export pump protein
  • CAcholic acid
  • CADcoronary artery disease
  • CARnuclear receptor subfamily 1 group I, member 2
  • CDCAchenodeoxycholic acid
  • CETPcholesterol ester transfer protein
  • COPIIproteins Sar1b, Sec23/24, and Sec13/31
  • CV cardiovascular
  • CYP7A1cholesterol 7α-hydroxylase
  • CYP27A1sterol 27-hydoxylase
  • DCAdeoxycholic acid
  • ERendoplasmic reticulum
  • ERCendocytic or endosomal recycling compartment
  • FABP6fatty acid-binding protein 6 gene
  • FGF19fibroblast growth factor-19
  • FGF4fibroblast growth factor-4
  • FLOT1flotillin-1
  • FXRfarnesoid X factor
  • GLP-1glucagon-like peptide
  • GPBAR1G-protein coupled bile acid receptor 1 gene
  • GPIHBP1glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1
  • HDLhigh density lipoprotein
  • HLhepatic lipase
  • HNF4αhepatocyte nuclear factor 4-α
  • HSLhormone sensitive lipase
  • IBABPfatty acid-binding protein 6 or ileal bile acid-binding protein
  • IDLintermediate density lipoprotein
  • IDOLinducible degrader of the LDL receptor
  • ISBTileal sodium/bile acid cotransporter
  • LALlysosomal acid lipase
  • LCAlithocholic acid
  • LCATlecithin cholesterol acyl transferase
  • DLlow density lipoprotein
  • LDLRAP1low density lipoprotein receptor adaptor protein 1
  • LIPAlysosomal acid lipase gene
  • LIPChepatic lipase gene
  • LMF1lipase maturation factor 1
  • LOX-1class E lectin-like oxidized low-density lipoprotein receptor-1
  • LPLlipoprotein lipase
  • LRPLDL receptor-related protein
  • LXRliver X receptor
  • MBTPS1membrane-bound transcription factor protease, site 1
  • MTPmicrosomal transfer protein
  • MTTPmicrosomal transfer protein gene
  • MYLIPinducible degrader of the LDL receptor gene
  • NPC1Niemann-Pick C1 protein
  • NPC1L1Niemann Pick C1-like 1
  • NR1H4farnesoid X factor gene
  • NR1I2nuclear receptor subfamily 1 group I, member 2 gene
  • NR1I3nuclear receptor subfamily 1 group I, member 3 gene
  • NR0B2nuclear receptor subfamily 0 group B, member 2 gene
  • NTCPsodium/bile acid cotransporter
  • OLR1Class E lectin-like oxidized low-density lipoprotein receptor-1 gene
  • OSBPoxysterol binding protein
  • OSTα/βsolute transporter alpha and beta
  • PCSK9proprotein convertase subtilisin/kexin type 9
  • PCTVpre-chylomicron transport vesicle
  • PLIN1perilipin-1
  • PLTPphospholipid transfer protein
  • PXRnuclear receptor subfamily 1 group I, member 2
  • SCAPSREBP cleavage-activating protein
  • SCARB1scavenger receptor class B member I gene
  • SHPnuclear receptor subfamily 0 group B, member 2
  • SLC10A1sodium/bile acid cotransporter gene
  • SLC10A2ileal sodium/bile acid cotransporter gene
  • SLC51Asolute transporter alpha gene
  • SLC51Bsolute transporter beta gene
  • SNAREV-soluble N-ethylmaleimide-sensitive factor attachment protein receptor
  • SOATsterol O-acyltransferase gene
  • SR-BIscavenger receptor class B member I
  • SREBP-2Sterol regulatory element-binding protein 2
  • TGR5G-protein coupled bile acid receptor 1
  • VDRvitamin D receptor
  • VLDLvery low density lipoproteins
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