Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 36, Issue 12, 2016, Pages 2439-2445

  Wang, Jian ^a   Dron, Jacqueline S ^a,b   Ban, Matthew R ^a   Robinson, John F ^a   McIntyre, Adam D ^a   Alazzam, Maher ^b   Zhao, Pei Jun ^a   Dilliott, Allison A ^a,b   Cao, Henian ^a   Huff, Murray W ^a,b   Rhainds, David ^d   Low Kam, Cécile ^d   Dubé, Marie Pierre ^c,d   Lettre, Guillaume ^c,d   Tardif, Jean Claude ^c,d   Hegele, Robert A ^a,b  

^a ROBARTS RESEARCH INSTITUTE   (Canada)

^b WESTERN UNIVERSITY   (Canada)

^c UNIVERSITÉ DE MONTRÉAL   (Canada)

^d MONTREAL HEART INSTITUTE   (Canada)

Author keywords

cholesterol, LDL; hypercholesterolemia type IIA; hyperlipoproteinemias; mutation; sequence analysis, DNA

Indexed keywords

ABC TRANSPORTER G5; ABC TRANSPORTER G8; APOLIPOPROTEIN B; APOLIPOPROTEIN E; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; TRIACYLGLYCEROL; BIOLOGICAL MARKER; GENETIC MARKER;

ADULT; AGED; ARTICLE; CHOLESTEROL BLOOD LEVEL; COHORT ANALYSIS; COPY NUMBER VARIATION; FAMILIAL HYPERCHOLESTEROLEMIA; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION; NEXT GENERATION SEQUENCING; NONSENSE MUTATION; PRIORITY JOURNAL; RNA SPLICING; SINGLE NUCLEOTIDE POLYMORPHISM; BLOOD; COMPARATIVE STUDY; DNA MUTATIONAL ANALYSIS; GENE DOSAGE; GENETIC MARKER; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; HEREDITY; HETEROZYGOTE; HIGH THROUGHPUT SEQUENCING; HYPERLIPOPROTEINEMIA TYPE II; MIDDLE AGED; MULTIFACTORIAL INHERITANCE; MUTATION; ONTARIO; PHENOTYPE; PREDICTIVE VALUE; PROCEDURES; RISK FACTOR; SEVERITY OF ILLNESS INDEX;

ADULT; AGED; BIOMARKERS; CHOLESTEROL, LDL; DNA COPY NUMBER VARIATIONS; DNA MUTATIONAL ANALYSIS; FEMALE; GENE DOSAGE; GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HEREDITY; HETEROZYGOTE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MALE; MIDDLE AGED; MULTIFACTORIAL INHERITANCE; MUTATION; ONTARIO; PHENOTYPE; PREDICTIVE VALUE OF TESTS; RISK FACTORS; SEVERITY OF ILLNESS INDEX;

EID: 84992046652     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.116.308027     Document Type: Article

References (20)

1. Nordestgaard BG, Chapman MJ, Humphries SE, et al; European Atherosclerosis Society Consensus Panel. 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. doi: 10.1093/eurheartj/eht273.
2. Benn M, Watts GF, Tybjarg-Hansen A, Nordestgaard BG. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37:1384-1394. doi: 10.1093/eurheartj/ehw028.
3. Do R, Stitziel NO, Won HH, et al; NHLBI Exome Sequencing Project. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015;518:102-106. doi: 10.1038/nature13917.
4. Khera AV, Won HH, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578-2589. doi: 10.1016/j.jacc.2016.03.520.
5. Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet. 2013;381:1293-1301. doi: 10.1016/S0140-6736(12)62127-8.
6. Hegele RA, Ban MR, Cao H, McIntyre AD, Robinson JF, Wang J. Targeted next-generation sequencing in monogenic dyslipidemias. Curr Opin Lipidol. 2015;26:103-113. doi: 10.1097/MOL.0000000000000163.
7. Wang J, Ban MR, Hegele RA. Multiplex ligation-dependent probe amplification of LDLR enhances molecular diagnosis of familial hypercholesterolemia. J Lipid Res. 2005;46:366-372. doi: 10.1194/jlr.D400030-JLR200.
8. Sniderman AD, Tsimikas S, Fazio S. The severe hypercholesterolemia phenotype: clinical diagnosis, management, and emerging therapies. J Am Coll Cardiol. 2014;63:1935-1947. doi: 10.1016/j.jacc.2014.01.060.
9. Hegele RA, Gidding SS, Ginsberg HN, McPherson R, Raal FJ, Rader DJ, Robinson JG, Welty FK. Nonstatin low-density lipoprotein-lowering therapy and cardiovascular risk reduction-statement from ATVB Council. Arterioscler Thromb Vasc Biol. 2015;35:2269-2280. doi: 10.1161/ATVBAHA.115.306442.
10. Hegele RA. Improving the monitoring and care of patients with familial hypercholesterolemia. J Am Coll Cardiol. 2016;67:1286-1288. doi: 10.1016/j.jacc.2016.01.041.
11. Samarakoon PS, Sorte HS, Stray-Pedersen A, Rødningen OK, Rognes T, Lyle R. cnvScan: a CNV screening and annotation tool to improve the clinical utility of computational CNV prediction from exome sequencing data. BMC Genomics. 2016;17:51. doi: 10.1186/s12864-016-2374-2.
12. Tybjaerg-Hansen A, Jensen HK, Benn M, Steffensen R, Jensen G, Nordestgaard BG. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations. Arterioscler Thromb Vasc Biol. 2005;25:211-215. doi: 10.1161/01.ATV.0000149380.94984.f0.
13. Futema M, Plagnol V, Whittall RA, Neil HA, Humphries SE; Simon Broome Register Group; UK10K. Use of targeted exome sequencing as a diagnostic tool for Familial Hypercholesterolaemia. J Med Genet. 2012;49:644-649. doi: 10.1136/jmedgenet-2012-101189.
14. Ahmad Z, Adams-Huet B, Chen C, Garg A. Low prevalence of mutations in known loci for autosomal dominant hypercholesterolemia in a multiethnic patient cohort. Circ Cardiovasc Genet. 2012;5:666-675. doi: 10.1161/CIRCGENETICS.112.963587.
15. Maglio C, Mancina RM, Motta BM, Stef M, Pirazzi C, Palacios L, Askaryar N, Borén J, Wiklund O, Romeo S. Genetic diagnosis of familial hypercholesterolaemia by targeted next-generation sequencing. J Intern Med. 2014;276:396-403. doi: 10.1111/joim.12263.
16. Norsworthy PJ, Vandrovcova J, Thomas ER, Campbell A, Kerr SM, Biggs J, Game L, Soutar AK, Smith BH, Dominiczak AF, Porteous DJ, Morris AD, Scotland G, Aitman TJ. Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study. BMC Med Genet. 2014;15:70. doi: 10.1186/1471-2350-15-70.
17. Cuchel M, Bruckert E, Ginsberg HN, et al; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35:2146-2157. doi: 10.1093/eurheartj/ehu274.
18. Futema M, Shah S, Cooper JA, et al. 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;61:231-238. doi: 10.1373/clinchem.2014.231365.
19. Stitziel NO, Peloso GM, Abifadel M, et al. Exome sequencing in suspected monogenic dyslipidemias. Circ Cardiovasc Genet. 2015;8:343-350. doi: 10.1161/CIRCGENETICS.114.000776.
20. Futema M, Plagnol V, Li K, et al; Simon Broome Consortium; UK10K Consortium. Whole exome sequencing of familial hypercholesterolaemia patients negative for LDLR/APOB/PCSK9 mutations. J Med Genet. 2014;51:537-544. doi: 10.1136/jmedgenet-2014-102405.