LDLR

Summary

Gene Symbol: LDLR
Description: low density lipoprotein receptor
Alias: FHC, LDLCQ2, low-density lipoprotein receptor, LDL receptor, low-density lipoprotein receptor class A domain-containing protein 3
Species: human
Products:     LDLR

Top Publications

  1. Zhang L, Yuan F, Liu P, Fei L, Huang Y, Xu L, et al. Association between PCSK9 and LDLR gene polymorphisms with coronary heart disease: case-control study and meta-analysis. Clin Biochem. 2013;46:727-32 pubmed publisher
    To explore the association of rs11206510 (PCSK9 gene) and rs1122608 (LDLR gene) polymorphisms with coronary heart disease (CHD) in Han Chinese...
  2. Maxwell K, Fisher E, Breslow J. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci U S A. 2005;102:2069-74 pubmed
    ..leads to increased total and low-density lipoprotein (LDL) cholesterol levels because of a decrease in hepatic LDL receptor (LDLR) protein with normal mRNA levels...
  3. Widhalm K, Dirisamer A, Lindemayr A, Kostner G. Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations. J Inherit Metab Dis. 2007;30:239-47 pubmed
    ..8 +/- 10.8 years). 119 patients with mutations have been detected; 56 children with either low density lipoprotein receptor (LDLR) and/or ApoB mutations (27 girls and 29 boys; mean total cholesterol (TC) 275 +/- 71 mg/dl, ..
  4. Ni Y, Condra J, Orsatti L, Shen X, Di Marco S, Pandit S, et al. A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J Biol Chem. 2010;285:12882-91 pubmed publisher
    PCSK9 binds to the low density lipoprotein receptor (LDLR) and leads to LDLR degradation and inhibition of plasma LDL cholesterol clearance...
  5. Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown M, Goldstein J, et al. Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002;298:2353-8 pubmed
    ..We propose a mechanism for lipoprotein release in the endosome whereby the beta propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release. ..
  6. Austin M, Hutter C, Zimmern R, Humphries S. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004;160:407-20 pubmed
    ..FH can result from mutations in the low density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), and the recently identified proprotein convertase ..
  7. Silva S, Alves A, Patel D, Malhó R, Soutar A, Bourbon M. In vitro functional characterization of missense mutations in the LDLR gene. Atherosclerosis. 2012;225:128-34 pubmed publisher
    Mutations in the LDL receptor gene are the major cause of familial hypercholesterolaemia (FH) but it has been previously shown that the simple finding of a variation in the coding sequence of the LDLR does not confirm that it is the ..
  8. Ahmed W, Ajmal M, Sadeque A, Whittall R, Rafiq S, Putt W, et al. Novel and recurrent LDLR gene mutations in Pakistani hypercholesterolemia patients. Mol Biol Rep. 2012;39:7365-72 pubmed publisher
    ..with the autosomal dominant disorder familial hypercholesterolemia (FH) carry novel mutations in the low density lipoprotein receptor (LDLR) that is involved in cholesterol regulation...
  9. Jones C, Hammer R, Li W, Cohen J, Hobbs H, Herz J. Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J Biol Chem. 2003;278:29024-30 pubmed
    ..As in FH, the rate of clearance of circulating low density lipoprotein (LDL) by the LDL receptor (LDLR) in the liver is markedly reduced in ARH...

More Information

Publications85

  1. Molina S, Castet V, Fournier Wirth C, Pichard Garcia L, Avner R, Harats D, et al. The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J Hepatol. 2007;46:411-9 pubmed
    The direct implication of low-density lipoprotein receptor (LDLR) in hepatitis C virus (HCV) infection of human hepatocyte has not been demonstrated. Normal primary human hepatocytes infected by serum HCV were used to document this point...
  2. Martinelli N, Girelli D, Lunghi B, Pinotti M, Marchetti G, Malerba G, et al. Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile. Blood. 2010;116:5688-97 pubmed publisher
    ..Low-density lipoprotein receptor (LDLR) has been recently demonstrated to contribute to FVIII clearance from plasma...
  3. Wang L, Lin J, Liu S, Cao S, Liu J, Yong Q, et al. Mutations in the LDL receptor gene in four Chinese homozygous familial hypercholesterolemia phenotype patients. Nutr Metab Cardiovasc Dis. 2009;19:391-400 pubmed publisher
    ..8mm. Our data demonstrated that all the probands were associated with severe hypercholesterolemia, thick carotid IMT and a low CFVR (coronary flow velocity reserve) value. The novel mutation (C120Y) is a disease causing mutation. ..
  4. Tejedor D, Castillo S, Mozas P, Jiménez E, Lopez M, Tejedor M, et al. Reliable low-density DNA array based on allele-specific probes for detection of 118 mutations causing familial hypercholesterolemia. Clin Chem. 2005;51:1137-44 pubmed
    ..Mutations in the LDL receptor (LDLR) gene and the R3500Q mutation in the apolipoprotein B (APOB) gene are known to cause FH, but lack of high-..
  5. Sanna S, Li B, Mulas A, Sidore C, Kang H, Jackson A, et al. Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability. PLoS Genet. 2011;7:e1002198 pubmed publisher
    ..To assess this hypothesis, we re-examined 7 genes (APOE, APOC1, APOC2, SORT1, LDLR, APOB, and PCSK9) in 5 loci associated with low-density lipoprotein cholesterol (LDL-C) in multiple GWAS...
  6. Taylor A, Wang D, Patel K, Whittall R, Wood G, Farrer M, et al. Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project. Clin Genet. 2010;77:572-80 pubmed publisher
    ..Six hundred and thirty-five probands from six UK centres were tested for 18 low-density lipoprotein receptor gene (LDLR) mutations, APOB p.Arg3527Gln and PCSK9 p...
  7. Nassoury N, Blasiole D, Tebon Oler A, Benjannet S, Hamelin J, Poupon V, et al. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic. 2007;8:718-32 pubmed
    ..proprotein convertase subtilisin kexin 9 (PCSK9) to elicit the degradation of the low-density lipoprotein receptor (LDLR) protein...
  8. Ramakrishnan G, Arjuman A, Suneja S, Das C, Chandra N. The association between insulin and low-density lipoprotein receptors. Diab Vasc Dis Res. 2012;9:196-204 pubmed publisher
    The insulin receptor (IR) and low-density lipoprotein receptor (LDLR) maintain glucose and lipid metabolism, respectively. Diabetes is associated with increased blood glucose, dyslipidaemia and increased risk of atherosclerosis...
  9. Damgaard D, Nissen P, Jensen L, Nielsen G, Stenderup A, Larsen M, et al. Detection of large deletions in the LDL receptor gene with quantitative PCR methods. BMC Med Genet. 2005;6:15 pubmed
    ..FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene...
  10. Pisciotta L, Priore Oliva C, Cefalù A, Noto D, Bellocchio A, Fresa R, et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis. 2006;186:433-40 pubmed
    Patients homozygous or compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels, more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple ..
  11. Bourbon M, Duarte M, Alves A, Medeiros A, Marques L, Soutar A. Genetic diagnosis of familial hypercholesterolaemia: the importance of functional analysis of potential splice-site mutations. J Med Genet. 2009;46:352-7 pubmed publisher
    Familial hypercholesterolemia (FH) results from defective low-density lipoprotein receptor (LDLR) activity, mainly due to LDLR gene defects...
  12. McNutt M, Kwon H, Chen C, Chen J, Horton J, Lagace T. Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J Biol Chem. 2009;284:10561-70 pubmed publisher
    ..receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. It is not known whether PCSK9 causes degradation of LDLRs within the secretory pathway or following secretion and ..
  13. Yamamoto T, Lu C, Ryan R. A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J Biol Chem. 2011;286:5464-70 pubmed publisher
    ..This multidomain protein interacts with the LDL receptor (LDLR), promoting receptor degradation...
  14. Lin J, Wang L, Liu S, Xia J, Yong Q, Du L, et al. Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C-->T mutation of low-density lipoprotein receptor gene. Chin Med J (Engl). 2008;121:776-81 pubmed
    ..The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China. ..
  15. Damgaard D, Larsen M, Nissen P, Jensen J, Jensen H, Soerensen V, et al. The relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population. Atherosclerosis. 2005;180:155-60 pubmed
    The genes encoding the LDL receptor and apoB were screened for mutations associated with familial hypercholesterolemia (FH) in 408 patients referred to the Lipid Clinic in 1995-2003...
  16. Cunningham D, Danley D, Geoghegan K, Griffor M, Hawkins J, Subashi T, et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol. 2007;14:413-9 pubmed
    ..Biosensor studies show that PCSK9 binds the extracellular domain of LDL receptor with K(d) = 170 nM at the neutral pH of plasma, but with a K(d) as low as 1 nM at the acidic pH of endosomes...
  17. Polisecki E, Muallem H, Maeda N, Peter I, Robertson M, McMahon A, et al. Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. Atherosclerosis. 2008;200:109-14 pubmed publisher
    ..to evaluate associations of single nucleotide polymorphisms (SNPs) at the low density lipoprotein (LDL) receptor (LDLR C44857T, minor allele frequency (MAF) 0.26, and A44964G, MAF 0...
  18. Sørensen S, Ranheim T, Bakken K, Leren T, Kulseth M. Retention of mutant low density lipoprotein receptor in endoplasmic reticulum (ER) leads to ER stress. J Biol Chem. 2006;281:468-76 pubmed
    ..hypercholesterolemia is an autosomal dominant disease caused by mutations in the gene encoding the low density lipoprotein receptor (LDLR)...
  19. Bartosch B, Dubuisson J, Cosset F. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med. 2003;197:633-42 pubmed
    ..Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry...
  20. Zakharova F, Damgaard D, Mandelshtam M, Golubkov V, Nissen P, Nilsen G, et al. Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia. BMC Med Genet. 2005;6:6 pubmed
    ..Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene mutations found in St...
  21. Duff C, Scott M, Kirby I, Hutchinson S, Martin S, Hooper N. Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009;419:577-84 pubmed publisher
    PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a ..
  22. Mayer G, Poirier S, Seidah N. Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem. 2008;283:31791-801 pubmed publisher
    The proprotein convertase subtilisin/kexin-type 9 (PCSK9), which promotes degradation of the hepatic low density lipoprotein receptor (LDLR), is now recognized as a major player in plasma cholesterol metabolism...
  23. Chen W, Wang S, Ma Y, Zhou Y, Liu H, Strnad P, et al. Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response. Int J Mol Med. 2008;21:345-53 pubmed
    The proximal section of the 3' untranslated region (3'UTR) of LDL receptor (LDLR) mRNA contains important regulatory sequences that control the messenger stability and mediate the cholesterol-lowering drug berberine (BBR)-induced increase ..
  24. Zelcer N, Hong C, Boyadjian R, Tontonoz P. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009;325:100-4 pubmed publisher
    ..LXR inhibits the LDL receptor (LDLR) pathway through transcriptional induction of Idol (inducible degrader of the LDLR), an E3 ubiquitin ..
  25. Mihaylov V, Horvath A, Savov A, Kurshelova E, Paskaleva I, Goudev A, et al. Screening for point mutations in the LDL receptor gene in Bulgarian patients with severe hypercholesterolemia. J Hum Genet. 2004;49:173-6 pubmed
    ..caused by defects in the receptor-mediated uptake of LDL (low-density lipoproteins) due to mutations in the LDL receptor gene ( LDLR). Mutations underlying FH in Bulgaria are largely unknown...
  26. Alonso R, Mata N, Castillo S, Fuentes F, Saenz P, Muniz O, et al. Cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors. Atherosclerosis. 2008;200:315-21 pubmed publisher
    ..1+/-14 years, 383 males and 428 females) with a molecular defect in the low-density lipoprotein receptor (LDLR) gene from the Spanish National FH Register. Prevalence of PCVD was 21.9% (30.2% in males and 14...
  27. Zou F, Gopalraj R, Lok J, Zhu H, Ling I, Simpson J, et al. Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease. Hum Mol Genet. 2008;17:929-35 pubmed
    ..Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in female human liver and in minigene-transfected HepG2 cells...
  28. Holla Ø, Teie C, Berge K, Leren T. Identification of deletions and duplications in the low density lipoprotein receptor gene by MLPA. Clin Chim Acta. 2005;356:164-71 pubmed
    ..ligation-dependent probe amplification (MLPA) and long-range PCR to detect large deletions/duplications in the LDL receptor gene...
  29. Humphries S, Whittall R, Hubbart C, Maplebeck S, Cooper J, Soutar A, et al. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet. 2006;43:943-9 pubmed
    To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically ..
  30. Seidah N, Poirier S, Denis M, Parker R, Miao B, Mapelli C, et al. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS ONE. 2012;7:e41865 pubmed publisher
    ..convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR)...
  31. Chmara M, Wasag B, Zuk M, Kubalska J, Wegrzyn A, Bednarska Makaruk M, et al. Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations. J Appl Genet. 2010;51:95-106 pubmed publisher
    ..hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9)...
  32. De Castro Orós I, Pampín S, Bolado Carrancio A, De Cubas A, Palacios L, Plana N, et al. Functional analysis of LDLR promoter and 5' UTR mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Mutat. 2011;32:868-72 pubmed publisher
    Familial hypercholesterolemia (FH) is a dominant disorder due to mutations in the LDLR gene. Several mutations in the LDLR promoter are associated with FH...
  33. Meshkov A, Stambol skiĭ D, Krapivner S, Bochkov V, Kukharchuk V, Malyshev P. [Low density lipoprotein receptor gene mutations in patients with clinical diagnosis of familial hypercholesterolemia.]. Kardiologiia. 2004;44:58-61 pubmed
    b>Low density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterolemia which is associated with elevated risk of ischemic heart disease...
  34. Alonso R, Defesche J, Tejedor D, Castillo S, Stef M, Mata N, et al. Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform. Clin Biochem. 2009;42:899-903 pubmed publisher
    ..Lipochip provides a reliable, fast and cheap alternative for the genetic testing of patients with clinically diagnosed FH. ..
  35. McKeown P, Merlini P, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334-41 pubmed publisher
    ..six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9)...
  36. Liu A, Zhan S, Li L, Hu Y, Cao W, Wu T, et al. [Association between AvaII exon 13 polymorphism at the LDL receptor gene different and serum lipid levels in normotensives and essential hypertensives in Shanghai]. Zhonghua Liu Xing Bing Xue Za Zhi. 2003;24:542-6 pubmed
    To investigate the AvaII polymorphism of low density lipoprotein receptor gene in both health and essential hypertension populations, and to evaluate the association of AvaII polymorphism with level of blood lipid...
  37. Zhang D, Garuti R, Tang W, Cohen J, Hobbs H. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A. 2008;105:13045-50 pubmed publisher
    ..is a secreted protein that controls plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor (LDLR)...
  38. Civeira F, Ros E, Jarauta E, Plana N, Zambon D, Puzo J, et al. Comparison of genetic versus clinical diagnosis in familial hypercholesterolemia. Am J Cardiol. 2008;102:1187-93, 1193.e1 pubmed publisher
    ..Genetic testing for low-density lipoprotein (LDL) receptor (LDLR) and apolipoprotein B (APOB) gene defects is the preferable diagnostic method, but the best phenotype indication to ..
  39. Futema M, Whittall R, Kiley A, Steel L, Cooper J, Badmus E, et al. Analysis of the frequency and spectrum of mutations recognised to cause familial hypercholesterolaemia in routine clinical practice in a UK specialist hospital lipid clinic. Atherosclerosis. 2013;229:161-8 pubmed publisher
    ..289 patients (272 probands) were screened sequentially over a 2-year period for mutations in LDLR, APOB and PCSK9 using standard molecular genetic techniques...
  40. Ajmal M, Ahmed W, Sadeque A, Ali S, Bokhari S, Ahmed N, et al. Identification of a recurrent insertion mutation in the LDLR gene in a Pakistani family with autosomal dominant hypercholesterolemia. Mol Biol Rep. 2010;37:3869-75 pubmed publisher
    ..In order to find the causative mutation in this family, direct sequencing of the low density lipoprotein receptor (LDLR) gene was performed...
  41. Saavedra Y, Day R, Seidah N. The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem. 2012;287:43492-501 pubmed publisher
    PCSK9 enhances the cellular degradation of the LDL receptor (LDLR), leading to increased plasma LDL cholesterol...
  42. Kosenko T, Golder M, Leblond G, Weng W, Lagace T. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem. 2013;288:8279-88 pubmed publisher
    ..type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver...
  43. Benjannet S, Hamelin J, Chretien M, Seidah N. Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem. 2012;287:33745-55 pubmed
    ..convertase PCSK9 is a major target in the treatment of hypercholesterolemia because of its ability bind the LDL receptor (LDLR) and enhance its degradation in endosomes/lysosomes...
  44. Bauerfeind A, Knoblauch H, Costanza M, Luganskaja T, Toliat M, Nurnberg P, et al. Concordant association of lipid gene variation with a combined HDL/LDL-cholesterol phenotype in two European populations. Hum Hered. 2006;61:123-31 pubmed
    ..This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach...
  45. Gopalraj R, Zhu H, Kelly J, Mendiondo M, Pulliam J, Bennett D, et al. Genetic association of low density lipoprotein receptor and Alzheimer's disease. Neurobiol Aging. 2005;26:1-7 pubmed
    The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, ..
  46. Gupta N, Fisker N, Asselin M, Lindholm M, Rosenbohm C, Ørum H, et al. A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS ONE. 2010;5:e10682 pubmed publisher
    ..PCSK9 accelerates the degradation of hepatic low density lipoprotein receptor (LDLR) and low levels of hepatic PCSK9 activity are associated with reduced levels of circulating LDL-..
  47. Gent J, Braakman I. Low-density lipoprotein receptor structure and folding. Cell Mol Life Sci. 2004;61:2461-70 pubmed
    ..The low-density lipoprotein receptor (LDLR) is the prototype of a large family of structurally homologous cell surface receptors, which fold in the ER and ..
  48. Chen K, Mu Y, Wang B, Guo Q, Lu Z, Dou J, et al. Two novel mutations 685del 1 and D129G in the low-density lipoprotein receptor gene in a compound heterozygote Chinese family with familial hypercholesterolemia. Metabolism. 2007;56:636-40 pubmed
    ..DNA analysis of the other family members showed that the 2 mutations should be respectively located in different alleles of the proband. Both of the 2 mutations have not been reported previously. ..
  49. Varret M, Abifadel M, Rabes J, Boileau C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet. 2008;73:1-13 pubmed
    ..More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated...
  50. He G, Gupta S, Yi M, Michaely P, Hobbs H, Cohen J. ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem. 2002;277:44044-9 pubmed
    ..hypercholesterolemia, a disorder caused by defective internalization of low density lipoprotein receptors (LDLR) in the liver...
  51. Santos P, Morgan A, Jannes C, Turolla L, Krieger J, Santos R, et al. Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2014;233:206-10 pubmed publisher
    Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly by LDLR mutations...
  52. Al Khateeb A, Zahri M, Mohamed M, Sasongko T, Ibrahim S, Yusof Z, et al. Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia. BMC Med Genet. 2011;12:40 pubmed publisher
    ..The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide ..
  53. Lo Surdo P, Bottomley M, Calzetta A, Settembre E, Cirillo A, Pandit S, et al. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 2011;12:1300-5 pubmed publisher
    ..PCSK9 (proprotein convertase subtilisin/kexin type 9) is a key regulator of low-density lipoprotein receptor (LDLR) levels and cardiovascular health. We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH...
  54. Tveten K, Strøm T, Berge K, Leren T. PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment. J Lipid Res. 2013;54:1560-6 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDL receptor (LDLR) at the cell surface and reroutes the internalized LDLR to intracellular degradation...
  55. Taylor A, Martin B, Wang D, Patel K, Humphries S, Norbury G. Multiplex ligation-dependent probe amplification analysis to screen for deletions and duplications of the LDLR gene in patients with familial hypercholesterolaemia. Clin Genet. 2009;76:69-75 pubmed publisher
    ..in patients with autosomal dominant hypercholesterolaemia is a mutation of the low-density lipoprotein receptor (LDLR) gene...
  56. Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt N, Roos C, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240-9 pubmed publisher
    ..The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors. ..
  57. Wang C, Zhou X, Zhou G, Han D, Zheng F. [Interaction of ApoE and LDL-R gene polymorphisms and alcohol drinking and smoking on coronary heart disease]. Zhonghua Yi Xue Za Zhi. 2004;84:554-8 pubmed
    To investigate the association between the ApoE and LDLR-R gene loci on coronary heart disease (CHD) and their interaction with alcohol drinking and smoking in Hans of Chinese...
  58. Yamada Y, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, et al. Association of polymorphisms of ABCA1 and ROS1 with hypertension in Japanese individuals. Int J Mol Med. 2008;21:83-9 pubmed
    ..polymorphism of ABCA1, the C-->G (Ser2229Cys) polymorphism of ROS1, the C-->T (Asn591Asn) polymorphism of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4, the C-->G and A-->C polymorphisms of ADIPOR1, and the -..
  59. Fryer J, DeMattos R, McCormick L, O Dell M, Spinner M, Bales K, et al. The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice. J Biol Chem. 2005;280:25754-9 pubmed
    ..The primary apoE receptor that regulates levels of apoE in the brain is unknown. We report that the low density lipoprotein receptor (LDLR) regulates the cellular uptake and central nervous system levels of astrocyte-derived apoE...
  60. Zhu H, Tucker H, Grear K, Simpson J, Manning A, Cupples L, et al. A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol. Hum Mol Genet. 2007;16:1765-72 pubmed
    ..Since mutations in low-density lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia, we evaluated whether LDLR SNPs may alter splicing efficiency ..
  61. Punzalan F, Sy R, Santos R, Cutiongco E, Gosiengfiao S, Fadriguilan E, et al. Low density lipoprotein--receptor (LDL-R) gene mutations among Filipinos with familial hypercholesterolemia. J Atheroscler Thromb. 2005;12:276-83 pubmed
    Familial Hypercholesterolemia (FH) is an autosomal dominant disease resulting from mutations of the LDL (LDLR) receptor gene leading to a diminished catabolism and elevated level of LDL cholesterol (LDL-C)...
  62. Simard L, Viel J, Lambert M, Paradis G, Levy E, Delvin E, et al. The Delta>15 Kb deletion French Canadian founder mutation in familial hypercholesterolemia: rapid polymerase chain reaction-based diagnostic assay and prevalence in Quebec. Clin Genet. 2004;65:202-8 pubmed
    ..has autosomal dominant familial hypercholesterolemia due to mutations in the low-density lipoprotein receptor (LDLR) gene. Screening for these mutations is hampered by their large number, except in founder populations...
  63. Romano M, Di Taranto M, D Agostino M, Marotta G, Gentile M, Abate G, et al. Identification and functional characterization of LDLR mutations in familial hypercholesterolemia patients from Southern Italy. Atherosclerosis. 2010;210:493-6 pubmed publisher
    Autosomal dominant hypercholesterolemias are due to defects in the LDL receptor (LDLR) gene, in the apolipoprotein B-100 gene or in the proprotein convertase subtilisin/kexin type 9 gene...
  64. Mozas P, Castillo S, Tejedor D, Reyes G, Alonso R, Franco M, et al. Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR. Hum Mutat. 2004;24:187 pubmed
    Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), an autosomal dominant inherited disorder associated with an increased risk of premature atherosclerosis...
  65. Cheng D, Huang R, Lanham I, Cathcart H, Howard M, Corder E, et al. Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease. J Med Genet. 2005;42:129-31 pubmed
    ..associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2...
  66. Koeijvoets K, Rodenburg J, Hutten B, Wiegman A, Kastelein J, Sijbrands E. Low-density lipoprotein receptor genotype and response to pravastatin in children with familial hypercholesterolemia: substudy of an intima-media thickness trial. Circulation. 2005;112:3168-73 pubmed
    ..Whether the type of LDL receptor mutation predicts the response to statin treatment is not yet established...
  67. Humphries S, Cranston T, Allen M, Middleton Price H, Fernandez M, Senior V, et al. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med (Berl). 2006;84:203-14 pubmed
    ..245 probands), using single-strand conformation polymorphism of all exons of the low-density lipoprotein receptor (LDLR) gene, 48 different pathogenic mutations were found in 62 probands (25%), while 7 (2...
  68. Lamsa R, Helisalmi S, Herukka S, Tapiola T, Pirttila T, Vepsalainen S, et al. Genetic study evaluating LDLR polymorphisms and Alzheimer's disease. Neurobiol Aging. 2008;29:848-55 pubmed
    ..The specific risk haplotype GTT was associated with an increased level of tau and ptau in both men and women. Our findings suggest that LDLR gene may be associated with AD risk and its CSF biomarkers, especially in women.
  69. Zhang D, Lagace T, Garuti R, Zhao Z, McDonald M, Horton J, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282:18602-12 pubmed
    ..convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of hepatic low density lipoprotein receptors (LDLR), the major route of clearance of circulating cholesterol...
  70. Zhou J, Luo H. Exploration of the relationship between phlegm-dampness constitution and polymorphism of low density lipoprotein receptor genes Pvu II and Ava II. Chin J Integr Med. 2007;13:170-4 pubmed
    To explore the polymorphism of low density lipoprotein receptor (LDL-R) genes Pvu II and Ava II in a population with phlegm-dampness constitution (PDC)...
  71. Ajmal M, Ahmed W, Akhtar N, Sadeque A, Khalid A, Benish Ali S, et al. A novel pathogenic nonsense triple-nucleotide mutation in the low-density lipoprotein receptor gene and its clinical correlation with familial hypercholesterolemia. Genet Test Mol Biomarkers. 2011;15:601-6 pubmed publisher
  72. Kwon H, Lagace T, McNutt M, Horton J, Deisenhofer J. Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A. 2008;105:1820-5 pubmed publisher
    ..The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Here, we describe the crystal structure of a complex between PCSK9 and the EGF-A domain of the LDLR...
  73. Miyake Y, Yamamura T, Sakai N, Miyata T, Kokubo Y, Yamamoto A. Update of Japanese common LDLR gene mutations and their phenotypes: Mild type mutation L547V might predominate in the Japanese population. Atherosclerosis. 2009;203:153-60 pubmed publisher
    We investigated the LDLR gene mutations in 205 unrelated Japanese FH (familial hypercholesterolemia) heterozygotes to see if there is a prevalence of common mutations in the Japanese population...
  74. Corder E, Huang R, Cathcart H, Lanham I, Parker G, Cheng D, et al. Membership in genetic groups predicts Alzheimer disease. Rejuvenation Res. 2006;9:89-93 pubmed
    ..latent classification statistical model; that is, grade-of-membership analysis, and genotypes for APOE, APOCI, LDLr, cystatin C, and cathepsin D (180 cases, 120 controls)...
  75. Nissen P, Damgaard D, Stenderup A, Nielsen G, Larsen M, Faergeman O. Genomic characterization of five deletions in the LDL receptor gene in Danish Familial Hypercholesterolemic subjects. BMC Med Genet. 2006;7:55 pubmed
    ..disease that is most frequently caused by mutations in the gene encoding the receptor for low density lipoproteins (LDLR)...
  76. Glynou K, Laios E, Drogari E, Tsaoussis V. Development of a universal chemiluminometric genotyping method for high-throughput detection of 7 LDLR gene mutations in Greek population. Clin Biochem. 2008;41:335-42 pubmed publisher
    Familial hypercholesterolemia (FH) is caused by mutations in the LDL receptor (LDLR) gene...