Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH)

Familial hypercholesterolemia basic panel [6 genes]:

  • It includes the 6 genes most commonly associated with familial hypercholesterolemia: LDLR, APOB, PCSK9, LDLRAP1, APOE and the main gene associated with statin-induced myopathy, SLCO1B1.
  • Aimed at patients with a strong suspicion of disease based on phenotypic characteristics.
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent
LDLRAPOBPSCK9LDLRAP1APOESLCO1B1

FH basic panel plus [5 genes + Pharma + Risk]:

  • Aimed at patients with a strong suspicion of disease based on phenotypic characteristics
  • It includes the 5 genes most commonly associated with familial hypercholesterolemia.
  • It allows assessing the potential adverse effects of conventional lipid-lowering treatments (statins and fibrates). It includes variants in 49 genes with pharmacogenetic relevance: ABCB1, AMPD1, CH25H, COQ2, CPT2, CYP2D6, CYP3A4, CYP3A5, NPC1L1, PYGM, RYR1, SLC22A8, SLCO1B1, ABCC2, ABCG2, ACE, ADAMTS1, CFAP44, CRP, CXCL5, CYBA, CYP19A1, CYP2C9, CYP7A1, F3, FABP1, FDPS, FMO3, GATM, GNB3, HLA-DRB1, HLA-G, HTR3B, HTR7, IL1B, IL6, KIF6, MMP3, MTHFR, NOS3, POR, RHOA, RYR2, SCAP, SREBF1, TLR4, TNF, UGT1A3, UGT1A9.
  • It allows for an evaluation of genetic susceptibility to coronary artery disease [50 variants].
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent

MONOGENIC FH (Basic) [5 genes]:
LDLR, APOB, PCSK9, LDLRAP1, APOE

+

PHARMACOGENETICS (Lipid-lowering drugs)

+

GENETIC RISK OF CORONARY ARTERY DISEASE

FH comprehensive panel [13 genes + Pharma + Risk]:

  • It includes the 5 main genes associated with FH, 8 additional genes associated with hypercholesterolemia with a probable monogenic etiology, and genetic variants included in the main risk scores for polygenic familial hypercholesterolemia.
  • It allows for differential diagnosis in patients whose main biochemical alteration is hypercholesterolemia.
  • It includes the LPA gene, in which variants conferring a risk of coronary heart disease have been described.
  • It allows estimating the risk of hypercholesterolemia with a polygenic etiology (1-2) in patients with a negative study, useful for an adequate post-test familial genetic counseling.
  • It allows assessing the potential adverse effects of conventional lipid-lowering treatments (statins and fibrates). It includes variants in 49 genes with pharmacogenetic relevance.
  • It allows for an evaluation of genetic susceptibility to coronary artery disease [50 variants].
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent

MONOGENIC FH (comprehensive) & POLYGENIC FH [13 genes]:
LDLR, LDLRAP1, ABCG8, LIPA, STAP1, APOB, APOE, CRABP2, LPA, PCSK9, ABCG5, EPHX2, PNPLA5

+

PHARMACOGENETICS (Lipid-lowering drugs)

+

GENETIC RISK OF CORONARY ARTERY DISEASE

  • It includes the 6 genes most commonly associated with familial hypercholesterolemia: LDLR, APOB, PCSK9, LDLRAP1, APOE and the main gene associated with statin-induced myopathy, SLCO1B1.
  • Aimed at patients with a strong suspicion of disease based on phenotypic characteristics.
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent
LDLRAPOBPSCK9LDLRAP1
APOESLCO1B1
  • Aimed at patients with a strong suspicion of disease based on phenotypic characteristics
  • It includes the 5 genes most commonly associated with familial hypercholesterolemia.
  • It allows assessing the potential adverse effects of conventional lipid-lowering treatments (statins and fibrates). It includes variants in 49 genes with pharmacogenetic relevance: ABCB1, AMPD1, CH25H, COQ2, CPT2, CYP2D6, CYP3A4, CYP3A5, NPC1L1, PYGM, RYR1, SLC22A8, SLCO1B1, ABCC2, ABCG2, ACE, ADAMTS1, CFAP44, CRP, CXCL5, CYBA, CYP19A1, CYP2C9, CYP7A1, F3, FABP1, FDPS, FMO3, GATM, GNB3, HLA-DRB1, HLA-G, HTR3B, HTR7, IL1B, IL6, KIF6, MMP3, MTHFR, NOS3, POR, RHOA, RYR2, SCAP, SREBF1, TLR4, TNF, UGT1A3, UGT1A9.
  • It allows for an evaluation of genetic susceptibility to coronary artery disease [50 variants].
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent

MONOGENIC FH (Basic) [5 genes]:
LDLR, APOB, PCSK9, LDLRAP1, APOE

+

PHARMACOGENETICS (Lipid-lowering drugs)

+

GENETIC RISK OF CORONARY ARTERY DISEASE

  • It includes the 5 main genes associated with FH, 8 additional genes associated with hypercholesterolemia with a probable monogenic etiology, and genetic variants included in the main risk scores for polygenic familial hypercholesterolemia.
  • It allows for differential diagnosis in patients whose main biochemical alteration is hypercholesterolemia.
  • It includes the LPA gene, in which variants conferring a risk of coronary heart disease have been described.
  • It allows estimating the risk of hypercholesterolemia with a polygenic etiology (1-2) in patients with a negative study, useful for an adequate post-test familial genetic counseling.
  • It allows assessing the potential adverse effects of conventional lipid-lowering treatments (statins and fibrates). It includes variants in 49 genes with pharmacogenetic relevance.
  • It allows for an evaluation of genetic susceptibility to coronary artery disease [50 variants].
  • Adequate coverage for structural variants or CNVs (copy number variants).
Study requisition form
Informed consent

MONOGENIC FH (comprehensive) & POLYGENIC FH [13 genes]:
LDLR, LDLRAP1, ABCG8, LIPA, STAP1, APOB, APOE, CRABP2, LPA, PCSK9, ABCG5, EPHX2, PNPLA5

+

PHARMACOGENETICS (Lipid-lowering drugs)

+

GENETIC RISK OF CORONARY ARTERY DISEASE

Nota genes
NOTES ON GENES
-> Priority genes: Genes where there is sufficient evidence (clinical and functional) to consider them as associated with the disease; they are included in clinical practice guidelines. -> Secondary genes: Genes related to the disease but with a lower level of evidence
or constituting sporadic cases. -> * Candidate genes: Without sufficient evidence in humans but potentially associated with the disease.

Patients with clinical suspicion that meet the following criteria:

  1. LDL cholesterol level >155 mg/dL.
  2. Early presentation of coronary, cerebrovascular, or peripheral artery disease (men <55 years and women <60 years).
  3. Tendon xanthomas or corneal arcus before 45 years of age.
  4. First-degree relatives with diagnosis of familial hypercholesterolemia.

For differential diagnosis in patients whose main biochemical alteration is hypercholesterolemia.

  • Talmud PJ, Shah S, Whittall R, Futema M, Howard P, Cooper JA, Harrison SC, Li K, Drenos F, Karpe F, Neil HA, Descamps OS, Langenberg C, Lench N, Kivimaki M, Whittaker J, Hingorani AD, Kumari M, Humphries SE. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet. 2013 Apr 13;381(9874):1293-301
  • Futema M, Shah S, Cooper JA, Li K, Whittall RA, Sharifi M, Goldberg O, Drogari E, Mollaki V, Wiegman A, Defesche J, D’Agostino MN, D’Angelo A, Rubba P, Fortunato G, Waluś-Miarka M, Hegele RA, Aderayo Bamimore M, Durst R, Leitersdorf E, Mulder MT, Roeters van Lennep JE, Sijbrands EJ, Whittaker JC, Talmud PJ, Humphries SE. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem. 2015 Jan;61(1):231-8.
  • Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG1, Cook NR, Chasman DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O, Orho-Melander M, Ridker PM, Kathiresan S. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med. 2016 Dec 15;375(24):2349-2358
  • 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;34:3478-3490ª
  • Genest J, Hegele RA, Bergeron J, Brophy J, Carpentier A, Couture P, Davignon J, Dufour R, Frohlich J, Gaudet D, Gupta M, Krisnamoorthy P, Mancini J,
    McCrindle B, Raggi P, Ruel I, St-Pierre J (rimary Panel). Canadian Cardiovascular Society position statement on familial hypercholesterolemia. Can J Cardiol. 2014 Dec;30(12):1471-81.
  • Familial hypercholesterolaemia: identification and management. NICE guidelines https://www.nice.org.uk/guidance/cg71
  • Guidelines for the Diagnosis and Management of Familial Hypercholesterolaemia. The Cardiac Society of Australia and New Zealand. http://www.csanz.edu.au/wp-content/uploads/2014/12/Familial-Hypercholesterolaemia_2013-November.pdf
  • Mata P, Alonso R, Ruiz A, Gonzalez-Juanatey JR, Badimón L, Díaz-Díaz JL, Muñoz MT, Muñiz O, Galve E, Irigoyen L, et al. Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso. Atención Primaria, Volume 47, Issue 1, Pages 56-65
  • Hopkins PN, Toth PP, Ballantyne CM, Rader DJ; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun; 5(3 Suppl):S9-17
  • Centers for disease control and prevention (CDC). Public health genomics. Tier 1. Familial hypercholesterolemia: https://www.cdc.gov/genomics/implementation/toolkit/fh_1.htm
  • FH foundation (US). https://thefhfoundation.org/fh-diagnosis-management-and-family-screening

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