Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia

Solanas-Barca, María; de Castro-Orós, Isabel; Mateo-Gallego, Rocío; Cofán, Montserrat; Plana, Nuria; Puzo, José; Burillo, Elena; Martín-Fuentes, Paula; Ros, Emilio; Masana, Luis; Pocoví, Miguel; Civeira, Fernando; Cenarro, Ana

doi:10.1016/j.atherosclerosis.2012.03.011

Cited by 74Lipid metabolism and disordersLipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and Lipoproteins

Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia

Solanas-Barca, María, de Castro-Orós, Isabel, Mateo-Gallego, Rocío, Cofán, Montserrat, Plana, Nuria, Puzo, José, Burillo, Elena, Martín-Fuentes, Paula +5 more·2012·Atherosclerosis

DOI 10.1016/j.atherosclerosis.2012.03.011

Open this paper in CoChat — free account

Abstract

Objective Rare mutations in the APOE gene, undetectable with the usual genotyping technique, are responsible for dominant familial dysbetalipoproteinemia (FD) and therefore could be easily misclassified as familial combined hyperlipidemia (FCHL). We aimed to identify APOE mutations associated with dominant combined hyperlipoproteinemia and to establish their frequency in subjects with a clinical diagnosis of FCHL. Methods and results In 279 unrelated subjects with FCHL in whom a functional LDLR mutation was excluded, sequencing of the entire APOE gene detected 9 carriers of a rare mutation: 5 subjects (1.8%) with the R136S mutation (arginine at residue 136 changed to serine) and 4 subjects (1.4%) with the p.Leu149del mutation, a 3-bp inframe deletion that results in the loss of leucine at position 149. Both genetic defects were detected with similar frequency (2.5% and 1.3%, respectively) in an independent group of 160 FCHL subjects from other locations in Spain. Family studies demonstrated cosegregation of these APOE mutations with hyperlipoproteinemia. R136S carriers showed dysbetalipoproteinemia, while the lipid phenotype of p.Leu149del carriers was IIa or IIb. Conclusions Rare APOE mutations are responsible for approximately 3.5% of FCHL cases in our population. APOE R136S and p.Leu149del induce autosomal dominant FD and a phenotype indistinguishable from FCHL, respectively.

Integrity signals

Registry

Crossref · 10.1016/j.atherosclerosis.2012.03.011

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The APOE p.Leu167del mutation was reported in subjects with FCHL and in the HC126 family reported here with a bona fide ADH.
“The APOE p.Leu167del mutation was reported in subjects with familial combined hyperlipidemia (FCHL, type III dyslipoproteinemia) (Solanas-Barca M et al. 2012) and in the HC126 family reported here with a bona fide ADH.”
From Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with theAPOEp.Leu167del Mutation (2013) · cites this paper as Solanas-Barca M et al. 2012
The APOE p.Leu167del mutation was reported in subjects with familial combined hyperlipidemia (FCHL).
“The APOE p.Leu167del mutation was also reported in subjects with familial combined hyperlipidemia (FCHL, type III dyslipoproteinemia) (Solanas-Barca M et al. 2012).”
From Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with theAPOEp.Leu167del Mutation (2013) · cites this paper as Solanas-Barca M et al. 2012
The APOE p.Leu167del mutation was previously reported associated with sea-blue histiocytosis and familial combined hyperlipidemia.
“previously reported associated with sea-blue histiocytosis and familial combined hyperlipidemia”
From Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with theAPOEp.Leu167del Mutation (2013) · cites this paper as Solanas-Barca M et al. 2012
APOE p.Leu167del (Leu149del) was originally reported to be associated with sea blue histiocytosis and familial combined hyperlipidemia.
“As another example of an APOE variant, APOE p.Leu167del (Leu149del) was originally reported to be associated with sea blue histiocytosis and familial combined hyperlipidemia115-117).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [117]
APOE p.Leu167del was also erroneously reported as APOE p.Leu149del.
“This variant was also erroneously reported as APOE p.Leu149del116, 117).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [117]

The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement
Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.169404 · Cited by 11,961 · see citing works
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981 · see citing works
Hyperlipidemia in Coronary Heart Disease II. GENETIC ANALYSIS OF LIPID LEVELS IN 176 FAMILIES AND DELINEATION OF A NEW INHERITED DISORDER, COMBINED HYPERLIPIDEMIA
Goldstein, J. L., Schrott, H. G., Hazzard, W. R., Bierman, E. L., & Motulsky, A. G. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107332 · Cited by 1,442 · see citing works
Association of apolipoprotein E genotypes with lipid levels and coronary risk
Bennet, A. M., Di Angelantonio, E., Ye, Z., Wensley, F., Dahlin, A., Ahlbom, A., Keavney, B., Collins, R., Wiman, B., de Faire, U., et al. (2007) · JAMA · doi:10.1001/jama.298.11.1300 · Cited by 794 · see citing works
Untitled work
(1985) · PubMed · Cited by 706 · see citing works
Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients
Goldberg, A. C., Hopkins, P. N., Toth, P. P., Ballantyne, C. M., Rader, D. J., Robinson, J. G., Daniels, S. R., Gidding, S. S., de Ferranti, S. D., Ito, M. K., et al. (2011) · Journal of clinical lipidology · doi:10.1016/j.jacl.2011.03.001 · Cited by 622 · see citing works
Familial lipoprotein disorders in patients with premature coronary artery disease.
Genest, J. J., Martin-Munley, S., McNamara, J. R., Ordovás, J. M., Jenner, J. L., Myers, R. H., Silberman, S. R., Wilson, P. W., Salem, D. N., & Schaefer, E. J. (1992) · Circulation · doi:10.1161/01.cir.85.6.2025 · Cited by 598 · see citing works
Hyperlipidemia in Coronary Heart Disease
Goldstein, J. L., HAzzmm, W. R., ScinoTT, H. G., Bierman, E. L., Levinski, M. J., & Campbell, E. D. (1973) · Cited by 471 · see citing works
Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions.
Lalazar, A., Weisgraber, K. H., Rall, S. C., Giladi, H., Innerarity, T. L., Levanon, A. Z., Boyles, J. K., Amit, B., Gorecki, M., & Mahley, R. W. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68957-4 · Cited by 209 · see citing works
Coronary Artery Disease Risk in Familial Combined Hyperlipidemia and Familial Hypertriglyceridemia
Hopkins, P. N., HEISS, G. M., Ellison, R. C., Province, M. A., Pankow, J. S., Eckfeldt, J. H., & Hunt, S. C. (2003) · Circulation · doi:10.1161/01.cir.0000081777.17879.85 · Cited by 205 · see citing works
Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.
Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R., & Carrell, R. W. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113096 · Cited by 159 · see citing works
Reliable Low-Density DNA Array Based on Allele-Specific Probes for Detection of 118 Mutations Causing Familial Hypercholesterolemia
Tejedor, D. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2004.045203 · Cited by 122 · see citing works
[Lipid profile of the Spanish population: the DRECE (diet and risk of cardiovascular disease in Spain) study. DRECE study group].
Gómez-Gerique, J. A., Gutiérrez-Fuentes, J. A., Montoya, M. T., Porres, A., Rueda, A., Avellaneda, A., & Rubio, M. Á. (1999) · PubMed · Cited by 121 · see citing works
Familial-combined hyperlipidaemia in very young myocardial infarction survivors (<=40 years of age)
Wiesbauer, F., Blessberger, H., Azar, D., Goliasch, G., Wagner, O. F., Gerhold, L., Huber, K., Widhalm, K., Abdolvahab, F., Sodeck, G. H., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp051 · Cited by 112 · see citing works
Small, dense LDL and elevated apolipoprotein B are the common characteristics for the three major lipid phenotypes of familial combined hyperlipidemia.
Ayyobi, A. F., McGladdery, S. H., McNeely, M. J., Austin, M. A., Motulsky, A. G., & Brunzell, J. D. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000077220.44620.9b · Cited by 103 · see citing works
Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date.
Gaddi, A. V., Cicero, A. F. G., Odoo, F. O., Poli, A. A., & Paoletti, R. (2007) · PubMed Central · Cited by 92 · see citing works
Frequency of Low-Density Lipoprotein Receptor Gene Mutations in Patients With a Clinical Diagnosis of Familial Combined Hyperlipidemia in a Clinical Setting
Civeira, F., Jarauta, E., Cenarro, A., García-Otín, A. L., Tejedor, D., Zambón, D., Mallén, M., Ros, E., & Pocovı́, M. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.06.050 · Cited by 84 · see citing works
Self-citation
Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseases.
Huang, Y. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833af368 · Cited by 82 · see citing works
Screening for Dysbetalipoproteinemia by Plasma Cholesterol and Apolipoprotein B Concentrations
Blom, D. J., O’Neill, F. H., & Marais, A. D. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2004.047001 · Cited by 57 · see citing works
Familial combined hyperlipidemia: upstream transcription factor 1 and beyond
Lee, J. C., Lusis, A. J., & Pajukanta, P. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000217890.54875.13 · Cited by 46 · see citing works
Incomplete dominance of type III hyperlipoproteinemia is associated with the rare apolipoprotein E2 (Arg136 → Ser) variant in multigenerational pedigree studies
Pocovi, M., Cenarro, A., Civeir, F., Myers, R. H., Casao, E., Esteban, M., & Ordovas, J. M. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)06745-0 · Cited by 42 · see citing works
Self-citation
Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia
Jarauta, E., Mateo‐Gállego, R., Gilabert, R., Plana, N., Junyent, M., de Groot, E., Cenarro, A., Masana, L., Ros, E., & Civeira, F. (2011) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2010.10.011 · Cited by 40 · see citing works
Self-citation
Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation
Faivre, L., Saugier-Veber, P., Pais de Barros, J.-P., Verges, B., Couret, B., Lorcerie, B., Thauvin, C., Charbonnier, F., Huet, F., Gambert, P., et al. (2005) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201480 · Cited by 34 · see citing works
Familial Splenomegaly: Macrophage Hypercatabolism of Lipoproteins Associated with Apolipoprotein E Mutation [Apolipoprotein E (Δ149 Leu)]
Nguyen, T. T., Kruckeberg, K. E., O’Brien, J. F., Ji, Z.-S., Karnes, P. S., Crotty, T. B., Hay, I. D., Mahley, R. W., & O’Brien, T. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6981 · Cited by 29 · see citing works
High Plasma Level of Remnant-Like Particles Cholesterol in Familial Combined Hyperlipidemia
Graaf, J. D., van der Vleuten, G. M., ter Avest, E., Dallinga‐Thie, G. M., & Stalenhoef, A. F. H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1973 · Cited by 26 · see citing works
Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia
Bredie, S. J. H., Vogelaar, J. M., Demacker, P. N. M., & Stalenhoef, A. F. H. (1996) · Atherosclerosis · doi:10.1016/0021-9150(96)05924-2 · Cited by 24 · see citing works
Mutations inHFECausing Hemochromatosis Are Associated with Primary Hypertriglyceridemia
Solanas-Barca, M., Mateo‐Gállego, R., Calmarza, P., Jarauta, E., Bea, A. M., Cenarro, A., & Civeira, F. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0814 · Cited by 22 · see citing works
Self-citation
Apolipoprotein E Polymorphism Influences Lipid Phenotypes in Chinese Families With Familial Combined Hyperlipidemia
Pei, W.-D., Zhang, Y., Sun, Y., Gu, Y., Wang, Y., Zhang, C., Zhang, J., Liu, L., Hui, R., Liu, Y., et al. (2006) · Circulation Journal · doi:10.1253/circj.70.1606 · Cited by 12 · see citing works
Polymorphisms of the apolipoprotein B and E genes and their possible roles in familial and non-familial combined hyperlipidaemia.
Houlston, R. S., Lewis, B., & Humphries, S. E. (1991) · PubMed · Cited by 10 · see citing works
New technologies for delineating and characterizing the lipid exome: prospects for understanding familial combined hyperlipidemia
Horswell, S. D., Ringham, H. E., & Shoulders, C. C. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800081-jlr200 · Cited by 9 · see citing works

Flagged first, then by citations

Sorted by citations

APOE gene variants in primary dyslipidemia
Khalil, Y. A., Rabès, J.-P., Boileau, C., & Varret, M. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.007 · Cited by 170 · see citing works
Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with theAPOEp.Leu167del Mutation
Marduel, M., Ouguerram, K., Serre, V., Bonnefont-Rousselot, D., Marques-Pinheiro, A., Erik Berge, K., Devillers, M., Luc, G., Lecerf, J.-M., Tosolini, L., et al. (2013) · Human Mutation · doi:10.1002/humu.22215 · Cited by 133 · see citing works
Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade
Gisterå, A., Ketelhuth, D. F. J., Malin, S., & Hansson, G. K. (2022) · Circulation Research · doi:10.1161/circresaha.122.320263 · Cited by 120 · see citing works
APOE p.Leu167del mutation in familial hypercholesterolemia
Awan, Z. A., Choi, H. Y., Stitziel, N. O., Ruel, I. L., Bamimore, M. A., Husa, R., Gagnon, M.-H., Wang, R.-H. L., Peloso, G. M., Hegele, R. A., et al. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.09.007 · Cited by 104 · see citing works
The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes
Cenarro, A., Etxebarria, A., de Castro-Orós, I., Stef, M., Bea, A. M., Palacios, L., Mateo-Gallego, R., Benito-Vicente, A., Ostolaza, H., Tejedor, T., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3874 · Cited by 100 · see citing works
Self-citation
Hyperlipoproteinemia Type 3: The Forgotten Phenotype
Hopkins, P. N., Brinton, E. A., & Nanjee, M. N. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0440-2 · Cited by 88 · see citing works
Dysbetalipoproteinaemia: A mixed hyperlipidaemia of remnant lipoproteins due to mutations in apolipoprotein E
Marais, A. D., Solomon, G. A. E., & Blom, D. J. (2014) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2013.870526 · Cited by 70 · see citing works
Familial combined hyperlipidemia and hyperlipoprotein(a) as phenotypic mimics of familial hypercholesterolemia: Frequencies, associations and predictions
Ellis, K. L., Pang, J., Chan, D. C., Hooper, A. J., Bell, D. A., Burnett, J. R., & Watts, G. F. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.08.011 · Cited by 57 · see citing works
Autosomal dominant familial dysbetalipoproteinemia: A pathophysiological framework and practical approach to diagnosis and therapy
Koopal, C., Marais, A. D., Westerink, J., & Visseren, F. L. J. (2017) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2016.10.001 · Cited by 53 · see citing works
The Genetic Basis of Hypertriglyceridemia
Carrasquilla, G. D., Christiansen, M. R., & Kilpeläinen, T. O. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00939-y · Cited by 54 · see citing works
Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France
Wintjens, R., Bozon, D., Belabbas, K., MBou, F., Girardet, J.-P., Tounian, P., Jolly, M., Boccara, F., Cohen, A., Karsenty, A., et al. (2016) · Journal of Lipid Research · doi:10.1194/jlr.p055699 · Cited by 47 · see citing works
Common Genetic Variants Contribute to Primary Hypertriglyceridemia Without Differences Between Familial Combined Hyperlipidemia and Isolated Hypertriglyceridemia
de Castro-Orós, I., Cenarro, A., Tejedor, M. T., Baila-Rueda, L., Mateo‐Gállego, R., Lamíquiz-Moneo, I., Pocovı́, M., & Civeira, F. (2014) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.114.000522 · Cited by 46 · see citing works
Self-citation
Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies
Taghizadeh, E., Esfehani, R. J., Sahebkar, A., Parizadeh, S. M., Rostami, D., Mirinezhad, M., Poursheikhani, A., Ghayour‐Mobarhan, M., & Pasdar, A. (2019) · IUBMB Life · doi:10.1002/iub.2073 · Cited by 45 · see citing works
Contribution of APOE Genetic Variants to Dyslipidemia
Bea, A. M., Larrea-Sebal, A., Marco-Benedi, V., Uribe, K. B., Galicia-Garcia, U., Lamiquiz-Moneo, I., Laclaustra, M., Moreno-Franco, B., Fernandez-Corredoira, P., Olmos, S., et al. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.123.318977 · Cited by 40 · see citing works
Self-citation
Genetic predictors of weight loss in overweight and obese subjects
Lamíquiz-Moneo, I., Mateo‐Gállego, R., Bea, A. M., Dehesa-García, B., Pérez‐Calahorra, S., Marco-Benedí, V., Baila-Rueda, L., Laclaustra, M., Civeira, F., & Cenarro, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-47283-5 · Cited by 39 · see citing works
Self-citation
Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population
Taranto, M. D. D., Staiano, A., D’Agostino, M. N., D’Angelo, A., Bloise, E., Morgante, A., Marotta, G., Gentile, M., Rubba, P., & Fortunato, G. (2014) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2014.10.002 · Cited by 39 · see citing works
Type III Hyperlipoproteinemia: Still Worth Considering?
Blum, C. B. (2016) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2016.07.007 · Cited by 39 · see citing works
ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols
Lamíquiz-Moneo, I., Baila-Rueda, L., Bea, A. M., Mateo‐Gállego, R., Pérez‐Calahorra, S., Marco-Benedí, V., Martín‐Navarro, A., Ros, E., Cofán, M., Rodríguez-Rey, J. C., et al. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.09.005 · Cited by 38 · see citing works
Self-citation
Disorders of Lipid Metabolism
Masood, S., Masood, O., Mujtaba, S. F., & Banerjee, M. (2024) · Springer eBooks · doi:10.1007/978-981-97-4723-8_4 · Cited by 31 · see citing works
Genes Potentially Associated with Familial Hypercholesterolemia
Михайлова, С. В., Иванощук, Д. Е., Тимощенко, О. В., & Шахтшнейдер, Е. В. (2019) · Biomolecules · doi:10.3390/biom9120807 · Cited by 25 · see citing works
Evaluation of the role of STAP1 in Familial Hypercholesterolemia
Danyel, M., Ott, C., Grenkowitz, T., Salewsky, B., Hicks, A. A., Fuchsberger, C., Steinhagen‐Thiessen, E., Bobbert, T., Kassner, U., & Demuth, I. (2019) · Scientific Reports · doi:10.1038/s41598-019-48402-y · Cited by 24 · see citing works
Lipoprotein(a) in hereditary hypercholesterolemia: Influence of the genetic cause, defective gene and type of mutation
Marco-Benedí, V., Cenarro, A., Laclaustra, M., Larrea, A., Jarauta, E., Lamíquiz-Moneo, I., Calmarza, P., Bea, A. M., Plana, N., Pintó, X., et al. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.08.009 · Cited by 24 · see citing works
Self-citation
Familial combined hyperlipidemia is a polygenic trait
Gill, P. K., & Hegele, R. A. (2021) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000796 · Cited by 24 · see citing works
Lipid-lowering response in subjects with the p.(Leu167del) mutation in the APOE gene
Bea, A. M., Lamíquiz-Moneo, I., Marco-Benedí, V., Mateo‐Gállego, R., Pérez‐Calahorra, S., Jarauta, E., Martı́n, C., Cenarro, A., & Civeira, F. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.01.024 · Cited by 23 · see citing works
Self-citation
APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia
Abou Khalil, Y., Marmontel, O., Ferrières, J., Paillard, F., Yelnik, C., Carreau, V., Charrière, S., Bruckert, E., Gallo, A., Giral, P., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105792 · Cited by 21 · see citing works
Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype
Bea, A. M., Cenarro, A., Marco-Bened, V., Laclaustra, M., Martn, C., Ibarretxe, D., Pint, X., Arrobas, T., Vials, C., Civeira, F., et al. (2023) · Clinical Chemistry · doi:10.1093/clinchem/hvac213 · Cited by 21 · see citing works
Self-citation
Exome Sequencing: New Insights into Lipoprotein Disorders
Farhan, S. M. K., & Hegele, R. A. (2014) · Current Cardiology Reports · doi:10.1007/s11886-014-0507-2 · Cited by 20 · see citing works
Association Between the Presence of Carotid Artery Plaque and Cardiovascular Events in Patients With Genetic Hypercholesterolemia
Bea, A. M., Civeira, F., Jarauta, E., Lamíquiz-Moneo, I., Pérez‐Calahorra, S., Marco-Benedí, V., Cenarro, A., & Mateo‐Gállego, R. (2017) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2017.01.023 · Cited by 20 · see citing works
Self-citation
Association between apolipoprotein gene polymorphisms and hyperlipidemia: a meta-analysis
Zhao, X., Sun, Q., Cao, Y.-Q., Ran, X., & Cao, Y. (2021) · BMC Genomic Data · doi:10.1186/s12863-021-00968-1 · Cited by 17 · see citing works
Cholesterol oversynthesis markers define familial combined hyperlipidemia versus other genetic hypercholesterolemias independently of body weight
Baila-Rueda, L., Cenarro, A., Lamíquiz-Moneo, I., Pérez‐Calahorra, S., Bea, A. M., Marco-Benedí, V., Jarauta, E., Mateo‐Gállego, R., & Civeira, F. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.10.005 · Cited by 17 · see citing works
Self-citation
Cosegregation of serum cholesterol with cholesterol intestinal absorption markers in families with primary hypercholesterolemia without mutations in LDLR, APOB, PCSK9 and APOE genes
Baila-Rueda, L., Pérez-Ruiz, M. R., Jarauta, E., Tejedor, M. T., Mateo‐Gállego, R., Lamíquiz-Moneo, I., de Castro-Orós, I., Cenarro, A., & Civeira, F. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.01.005 · Cited by 16 · see citing works
Self-citation
Effect of Nicotinic acid/Laropiprant in the lipoprotein(a) concentration with regard to baseline lipoprotein(a) concentration and LPA genotype
Cenarro, A., Puzo, J., Ferrando, J., Mateo‐Gállego, R., Bea, A. M., Calmarza, P., Jarauta, E., & Civeira, F. (2013) · Metabolism · doi:10.1016/j.metabol.2013.10.014 · Cited by 15 · see citing works
Self-citation
Asociación de la presencia de placa carotídea en la aparición de eventos cardiovasculares en pacientes con hipercolesterolemias genéticas
Bea, A. M., Civeira, F., Jarauta, E., Lamíquiz-Moneo, I., Pérez‐Calahorra, S., Marco-Benedí, V., Cenarro, A., & Mateo‐Gállego, R. (2016) · Revista Española de Cardiología · doi:10.1016/j.recesp.2016.10.018 · Cited by 15 · see citing works
Self-citation
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14 · see citing works
Rare genetic variants with large effect on triglycerides in subjects with a clinical diagnosis of familial vs nonfamilial hypertriglyceridemia
de Castro-Orós, I., Civeira, F., Pueyo, M. J., Mateo‐Gállego, R., Bolado‐Carrancio, A., Lamíquiz-Moneo, I., Álvarez-Sala, L., Romero, F. F., Cofán, M., Cenarro, A., et al. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.02.010 · Cited by 14 · see citing works
Self-citation
ANGPTL3 gene variants in subjects with familial combined hyperlipidemia
Bea, A. M., Franco-Marín, E., Marco-Benedí, V., Jarauta, E., Gracia‐Rubio, I., Cenarro, A., Civeira, F., & Lamíquiz-Moneo, I. (2021) · Scientific Reports · doi:10.1038/s41598-021-86384-y · Cited by 14 · see citing works
Self-citation
Apolipoprotein E4 allele is associated with substantial changes in the plasma lipids and hyaluronic acid content in patients with nonalcoholic fatty liver disease.
Stachowska, E., Maciejewska, D., Ossowski, P., Drozd, A., Ryterská, K., Banaszczak, M., Milkiewicz, M., Raszeja‐Wyszomirska, J., Ślebioda, M., Milkiewicz, P., et al. (2013) · PubMed · Cited by 14 · see citing works
APOE and familial hypercholesterolemia
Civeira, F., Martı́n, C., & Cenarro, A. (2024) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000937 · Cited by 13 · see citing works
Self-citation
Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE
Jarauta, E., Pérez-Ruiz, M. R., Pérez‐Calahorra, S., Mateo‐Gállego, R., Cenarro, A., Cofán, M., Ros, E., Civeira, F., & Tejedor, M. T. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.09.011 · Cited by 13 · see citing works
Self-citation
Association between non-cholesterol sterol concentrations and Achilles tendon thickness in patients with genetic familial hypercholesterolemia
Baila-Rueda, L., Lamíquiz-Moneo, I., Jarauta, E., Mateo‐Gállego, R., Pérez‐Calahorra, S., Marco-Benedí, V., Bea, A. M., Cenarro, A., & Civeira, F. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1380-3 · Cited by 12 · see citing works
Self-citation
Resequencing the APOE gene reveals that rare mutations are not significant contributory factors in the development of type III hyperlipidemia
Evans, D., Beil, F. U., & Aberle, J. (2013) · Journal of clinical lipidology · doi:10.1016/j.jacl.2013.05.003 · Cited by 12 · see citing works
Importance of the triglyceride level in identifying patients with a Type III Hyperlipoproteinemia phenotype using the ApoB algorithm
Varghese, B., Park, J., Chew, E., Sajja, A., Brownstein, A., Pallazola, V. A., Sathiyakumar, V., Jones, S. R., Sniderman, A. D., & Martin, S. S. (2021) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2020.09.011 · Cited by 12 · see citing works
Single Nucleotide Variants Associated With Polygenic Hypercholesterolemia in Families Diagnosed Clinically With Familial Hypercholesterolemia
Lamíquiz-Moneo, I., Pérez-Ruiz, M. R., Jarauta, E., Tejedor, M. T., Bea, A. M., Mateo‐Gállego, R., Pérez‐Calahorra, S., Baila-Rueda, L., Marco-Benedí, V., de Castro-Orós, I., et al. (2017) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2017.07.010 · Cited by 11 · see citing works
Self-citation
Functional analysis of new 3′ untranslated regions genetic variants in genes associated with genetic hypercholesterolemias
Pérez-Campo, F. M., de Castro-Orós, I., Noriega, A., Cofán, M., Lamíquiz-Moneo, I., Cenarro, A., Ros, E., Civeira, F., Pocovı́, M., & Rodríguez-Rey, J. C. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.02.004 · Cited by 10 · see citing works
Self-citation
Variantes de un solo nucleótido asociadas con la hipercolesterolemia poligénica en familias diagnosticadas de hipercolesterolemia familiar
Lamíquiz-Moneo, I., Pérez-Ruiz, M. R., Jarauta, E., Tejedor, M. T., Bea, A. M., Mateo‐Gállego, R., Pérez‐Calahorra, S., Baila-Rueda, L., Marco-Benedí, V., de Castro-Orós, I., et al. (2017) · Revista Española de Cardiología · doi:10.1016/j.recesp.2017.07.030 · Cited by 10 · see citing works
Self-citation
Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del mutation phenotypic variation
Okorodudu, D. E., Crowley, M. J., Sebastian, S., Rowell, J. V., & Guyton, J. R. (2013) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.09.003 · Cited by 9 · see citing works
Bile acid synthesis precursors in subjects with genetic hypercholesterolemia negative for LDLR/APOB/PCSK9/APOE mutations. Association with lipids and carotid atherosclerosis
Baila-Rueda, L., Cenarro, A., Lamíquiz-Moneo, I., Mateo‐Gállego, R., Bea, A. M., Pérez‐Calahorra, S., Marco-Benedí, V., & Civeira, F. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.10.003 · Cited by 7 · see citing works
Self-citation
Genetics of Familial Combined Hyperlipidemia (FCHL) Disorder: An Update
Taghizadeh, E., Farahani, N., Mardani, R., Taheri, F., Taghizadeh, H., & Hayat, S. M. G. (2021) · Biochemical Genetics · doi:10.1007/s10528-021-10130-2 · Cited by 7 · see citing works
Impact of rare variants in autosomal dominant hypercholesterolemia causing genes
Calandra, S., Tarugi, P., & Bertolini, S. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000414 · Cited by 7 · see citing works
The fine line between familial and polygenic hypercholesterolemia
de Castro-Orós, I., Pocovı́, M., & Civeira, F. (2013) · Clinical Lipidology · doi:10.2217/clp.13.20 · Cited by 6 · see citing works
Self-citation
APOE Genotype and Endothelial Biomarkers: Towards Personalized Cardiovascular Screening
Titolo, G., Morello, M., Caiazza, S., Luisi, E., Solimene, A., Serpico, C., D’Elia, S., Golino, P., Loffredo, F. S., Natale, F., et al. (2025) · Genes · doi:10.3390/genes16121494 · Cited by 5 · see citing works
Hiperlipemia familiar combinada/hiperlipemia mixta poligénica
Pedro‐Botet, J., Climent, E., Gabarro, N., & Millán, J. (2021) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2020.12.013 · Cited by 5 · see citing works
Leu22_Leu23 Duplication at the Signal Peptide of PCSK9 Promotes Intracellular Degradation of LDLr and Autosomal Dominant Hypercholesterolemia
Benito‐Vicente, A., Uribe, K. B., Larrea, A., Palacios, L., Cenarro, A., Calle, X., Galicia-García, U., Jebari‐Benslaiman, S., Sánchez-Hernández, R. M., Stef, M. A., et al. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.122.315499 · Cited by 5 · see citing works
Self-citation
Exploring of blood viscosity in injured liver tissues of hyperlipidemic mice
Liu, C., Yin, J., Lu, B., & Lin, W. (2022) · Dyes and Pigments · doi:10.1016/j.dyepig.2022.110272 · Cited by 5 · see citing works
Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and “Missing” Heritability
Martín-Campos, J. M. (2021) · Biomedicines · doi:10.3390/biomedicines9111728 · Cited by 4 · see citing works
Factors associated with the presence of tendon xanthomas in familial hypercholesterolemia
Corredoira, P. M. F., Marco-Benedí, V., Cenarro, A., Belanche, S. P., Olmos, S. C., & Civeira, F. (2024) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2023.12.003 · Cited by 4 · see citing works
Self-citation
Prediction of single nucleotide polymorphisms (SNPs) in apolipoprotein E gene and their possible associations with a deleterious effect on the structure and functional properties: an in silico approach
Saeed, N. A.-H. A. A. H., Hamzah, I. H., Ali, A. N. M., & Abuderman, A. (2018) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-018-0178-9 · Cited by 3 · see citing works
APOE p.(Leu167del) variant in hypercholesterolemia: Prevalence & phenotypic expression
Bello-Álvarez, D., Cenarro, A., Bea, A. M., Marco-Benedí, V., Jarauta, E., Ortiz-Palma, P., Ortega, E., González-Lleó, A. M., & Civeira, F. (2025) · Journal of clinical lipidology · doi:10.1016/j.jacl.2025.09.016 · Cited by 2 · see citing works
Self-citation
Effects of Long- and Short-term Darbepoetin-α Treatment on Oxidative Stress, Inflammation and Endothelial Injury in Apo E Knockout Mice
Özdemіr, E., Hanikoglu, A., Çört, A., Özben, B., Süleymanlar, G., & Özben, T. (2017) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/62834 · Cited by 2 · see citing works
Factores asociados a la presencia de xantomas tendinosos en la hipercolesterolemia familiar
Corredoira, P. M. F., Marco-Benedí, V., Cenarro, A., Belanche, S. P., Olmos, S. C., & Civeira, F. (2024) · Revista Española de Cardiología · doi:10.1016/j.recesp.2023.12.010 · Cited by 2 · see citing works
Self-citation
Omega-3 Polyunsaturated Fatty Acids and Hyperlipidaemias
Ferguson, J. J. A., Dias, C. B., & Garg, M. L. (2016) · Springer eBooks · doi:10.1007/978-3-319-40458-5_6 · Cited by 2 · see citing works
Evaluation of missense SNVs within human APOE (Apolipoprotein E) gene via bioinformatics tools
Karasakal, Ö. F., Oktay, E. Ö., & Kaman, T. (2023) · Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi · doi:10.25092/baunfbed.1197932 · Cited by 2 · see citing works
Disbetalipoproteinemia y otras alteraciones relacionadas con la apolipoproteína E
Cenarro, A., Bea, A. M., Gracia‐Rubio, I., & Civeira, F. (2021) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2021.01.002 · Cited by 2 · see citing works
Self-citation
Diagnosis of familial dysbetalipoproteinemia due to APOE p.(Arg154Ser): The role of ultracentrifugation and lipid ratios
Guerra-Ruiz, A. R., Millan, M. M., Bolt, Á. D. R., Gómez, B. A. L., & Hernández, J. L. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.05.241 · Cited by 1 · see citing works
Genetic screening to improve the diagnosis of familial hypercholesterolemia
Faiz, F., Nguyen, L., BOCKXMEER, F. M. V., & Hooper, A. J. (2014) · Clinical Lipidology · doi:10.2217/clp.14.32 · Cited by 1 · see citing works
Rare monogenic disorders of cholesterol metabolism
Bednarska‐Makaruk, M., & Ługowska, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85857-1.00024-9 · Cited by 1 · see citing works
Molecular investigation of familial hypercholesterolaemia: from gene to genome
Faiz, F. (2014) · UWA Profiles and Research Repository (UWA)
Bioinformatic Annotation of Genes for Alzheimer’s Disease and Coronary Heart Disease
Chasovskikh, N. Y., Chizhik, E. E., & Bobrysheva, A. A. (2021) · Russian Journal of Genetics · doi:10.1134/s102279542111003x
Monogenic Hypercholesterolemias
Civeira, F., & Pocovı́, M. (2015) · Contemporary Endocrinology · doi:10.1007/978-1-60761-424-1_10
Self-citation
Estudio molecular de los polimorfismos comunes del gen apoE asociados con disbetalipoproteinemia familiar y la enfermedad de Alzheimer de inicio tardío
(2023) · doi:10.46994/ets_36
Familial combined hyperlipidemia: current status of the problem (literature review)
Тимощенко, О. В., & Шахтшнейдер, Е. В. (2024) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2024-5874
Molecular dynamics of select missense mutations of Apolipoprotein E and their implications in Hyperlipoproteinemia type III
Thakur, S., Singh, B., & Singh, R. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.102190
Genetic causes of cardiovascular disease : special focus on familial hypercholesterolemia and thoracic aortic aneurysms
Elbitar, S. (2018) · theses.fr (ABES) · doi:10.70675/0d164341z4f5cz438cz9edazc7cc446db7a4
Abstract 13801: The p.Leu167del Mutation in APOE Gene causes Autosomal Dominant Hypercholesterolemia by Down-Regulation of LDL Receptor Expression in Hepatocytes
Cenarro, A., Martı́n, C., Stef, M. A., de Castro-Orós, I., Etxebarria, A., Palacios, L., Mateo‐Gállego, R., Ostolaza, H., Tejedor, M. T., & Civeira, F. (2014) · Circulation · doi:10.1161/circ.130.suppl_2.13801
Self-citation

Abstract 18248: Apolipoprotein E Gene Mutations in Subjects with Mixed Hyperlipoproteinemia and a Clinical Diagnosis of Familial Combined Hyperlipidemia
Solanas-Barca, M., de Castro-Orós, I., Bea, A. M., Cofán, M., Plana, N., Ros, E., Masana, L., Puzo, J., Pocovı́, M., Civeira, F., et al. (2011) · Circulation · doi:10.1161/circ.124.suppl_21.a18248
Self-citation
APOE1 mutation in a patient with type III hyperlipoproteinaemia: detailed genetic analysis required.
Visser, M. E., Dallinga‐Thie, G. M., Pinto‐Sietsma, S., Defesche, J. C., Stroes, E. S. G., & van der Valk, P. R. (2012) · PubMed · Cited by 9 · see citing works
Frequency of Low-Density Lipoprotein Receptor Gene Mutations in Patients With a Clinical Diagnosis of Familial Combined Hyperlipidemia in a Clinical Setting
Civeira, F., Jarauta, E., Cenarro, A., García-Otín, A. L., Tejedor, D., Zambón, D., Mallén, M., Ros, E., & Pocovı́, M. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.06.050 · Cited by 84 · see citing works
Self-citation
Identification of two rare APOE mutations associated with Familial Hypercholesterolaemia in the north of England
McAnulty, C., Boras, S., Curtis, A., Chaston, R., Stevenson, E., Bourn, D., Fairgrieve, S., Anderson, M., Burns, M., & Neely, R. D. G. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.10.032 · Cited by 1 · see citing works
Abstract 336: Overrepresentation of Familial Hypercholesterolemia-causing Mutations in Patients with Familial Combined Hyperlipidemia
Bamimore, M. A., Cao, H., Wang, J., McIntyre, A. D., Johansen, C., & Hegele, R. A. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvb.33.suppl_1.a336

Authors: Solanas-Barca, M., de Castro-Orós, I., Mateo-Gallego, R., Cofán, M., Plana, N., Puzo, J., Burillo, E., Martín-Fuentes, P., Ros, E., Masana, L., Pocoví, M., Civeira, F., & Cenarro, A.
Affiliations: Hospital Universitario Miguel Servet (ES)
Instituto de Salud Carlos III (ES)
Hospital General San Jorge (ES)
Corresponding author: Cenarro, Ana
ORCID: Cofán, Montserrat
Puzo, José
Ros, Emilio
Masana, Luis
Civeira, Fernando
Cenarro, Ana
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 2012-06
Volume: 222
Issue: 2
Pages: 449-455
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/j.atherosclerosis.2012.03.011
OpenAlex: W2085921423
Cited by: 74
References: 32
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 11 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 11 · 2015: 1 · 2014: 8 · 2013: 6 · 2012: 1
FWCI: 3.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (publishedVersion)
PubMed (publishedVersion)
Funders: Spanish Ministry of Health (FIS PS09/0673, FIS PS09/0665, FIS PI10/00387, RETIC C06/01 RD06/0014/0029)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: apolipoprotein E, familial combined hyperlipidemia, familial dysbetalipoproteinemia, mixed dyslipidemia, autosomal dominant inheritance, co-segregation, misdiagnosis, lipid phenotypes
MeSH terms: Adult, Analysis of Variance, Apolipoproteins E, DNA Mutational Analysis, Female, Gene Frequency, Humans, Hyperlipoproteinemia Type II, Hyperlipidemia, Familial Combined, Male, Middle Aged, Mutation, Pedigree, Phenotype, Receptors, LDL, Spain, Chi-Square Distribution, Odds Ratio, Genetic Predisposition to Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks