Screening for Rare Genetic Variants Associated with Atherosclerosis: Opportunity for Personalized Medicine

Author(s): Ana Peterlin, Daniel Petrovič, Borut Peterlin*

Journal Name: Current Vascular Pharmacology

Volume 17 , Issue 1 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Atherosclerosis and its clinical manifestations is a leading cause of disease burden worldwide. Currently, most of the individuals carrying a strong predisposition to complications of atherosclerosis because of monogenic dyslipidaemias remain undiagnosed and consequently are not given an opportunity for prevention. Therefore, one of the main public health challenges remains the identification of individuals with significantly increased risk for atherosclerosis due to monogenic predisposition. Next-Generation Sequencing (NGS) has revolutionized genetic testing in symptomatic patients. Although new genomic technologies are still developing, and evidence on the use of this methodology for screening purposes is still lacking, genome testing might provide a powerful tool for the identification of individuals at risk. This may pave the way for the implementation of personalized medicine in the field of atherosclerosis prevention.

In this review, we discuss the potential of genetic screening for atherosclerosis prevention and present the potential target of 17 genes responsible for monogenic dyslipidaemias associated with atherosclerosis.

Keywords: Atherosclerosis, coronary artery disease, cerebrovascular disease, screening, next generation sequencing, public health genomics, monogenic dyslipidaemia.

Lopez AD, Murray CC. The global burden of disease. 1990-2020. Nat Med 1998; 4(11): 1241-3.
De Backer G, Perk J, Gohlke H, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 2012; 33(13): 1635-701.
Paynter NP, Ridker PM, Chasman DI. Are genetic tests for atherosclerosis ready for routine clinical use? Circ Res 2016; 118(4): 607-19.
Bilen O, Pokharel Y, Ballantyne CM. Genetic testing in hyperlipidemia. Endocrinol Metab Clin North Am 2016; 45(1): 129-40.
Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. Eur Heart J 2017; 38(32): 2459-72.
Sharma K, Baliga RR. Genetics of dyslipidemia and ischemic heart disease. Curr Cardiol Rep 2017; 19(5): 46.
Leigh S, Futema M, Whittall R, et al. The UCL low-density lipoprotein receptor gene variant database: Pathogenicity update. J Med Genet 2017; 54(4): 217-23.
Ales M, Luca L, Marija V, et al. Phenotype-driven gene target definition in clinical genome-wide sequencing data interpretation. Genet Med 2016; 18(11): 1102-10.
Bergant G, Maver A, Lovrecic L, Čuturilo G, Hodzic A, Peterlin B. Comprehensive use of extended exome analysis improves diagnostic yield in rare disease: A retrospective survey in 1,059 cases. Genet Med 2018; 20(3): 303-12.
Hegele RA, Ban MR, Cao H, McIntyre AD, Robinson JF, Wang J. Targeted next-generation sequencing in monogenic dyslipidemias. Curr Opin Lipidol 2015; 26(2): 103-13.
Lindor NM, Thibodeau SN, Burke W. Whole-genome sequencing in healthy people. Mayo Clin Proc 2017; 92(1): 159-72.
Friedman JM, Cornel MC, Goldenberg AJ, et al. Genomic newborn screening: Public health policy considerations and recommendations. BMC Med Genomics 2017; 10(1): 9.
Landau YE, Lichter-Konecki U, Levy HL. Genomics in newborn screening. J Pediatr 2014; 164(1): 14-9.
Henneman L, Borry P, Chokoshvili D, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016; 24(6): 1-12.
Scheuner MT, Wang SJ, Raffel LJ, Larabell SK, Rotter JI. Family history: A comprehensive genetic risk assessment method for the chronic conditions of adulthood. Am J Med Genet 1997; 71(3): 315-24.
Klemenc-Ketiš Z, Peterlin B. Family history as a predictor for disease risk in healthy individuals: A cross-sectional study in Slovenia. PLoS One 2013; 8: e80333.
Natarajan P, Young R, Stitziel NO, et al. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation 2017; 135(22): 2091-101.
Assimes TL, Goldstein BA. Genetic cardiovascular risk prediction: Are we already there? Eur Heart J 2016; 37(43): 3279-81.
Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the Danish general population: Prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab 2012; 97(11): 3956-64.
Gidding SS, Champagne MA, De Ferranti SD, et al. The agenda for familial hypercholesterolemia: A scientific statement from the american heart association. Circulation 2015; 132(22): 2167-92.
Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia. JAMA 2016; 316(6): 634.
Daskalopoulou SS, Mikhailidis DP. Time for new low density lipoprotein cholesterol (LDL-C) targets? Expert Opin Pharmacother 2017; 18(15): 1539-41.
Braamskamp MJAM, Langslet G, McCrindle BW, et al. Effect of rosuvastatin therapy on carotid intima media thickness in children with familial hypercholesterolemia: Findings from the charon study. Atherosclerosis 2014; 235(2): 18-9.
Martin AC, Gidding SS, Wiegman A, Watts GF. Knowns and unknowns in the care of pediatric familial hypercholesterolemia. J Lipid Res 2017; 58(9): 1765-76.
Ademi Z, Watts GF, Juniper A, Liew D. A systematic review of economic evaluations of the detection and treatment of familial hypercholesterolemia. Int J Cardiol 2013; 167(6): 2391-6.
Knowles JW, Rader DJ, Khoury MJ. Cascade screening for familial hypercholesterolemia and the use of genetic testing. JAMA 2017; 318(4): 381-2.
Ned RM, Sijbrands E. Cascade screening for familial hypercholesterolemia (FH). PLoS Curr 2011; 3: 1238.
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. Eur Heart J 2013; 34(45): 3478-90.
Abul-Husn NS, Manickam K, Jones LK, et al. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science 2016; 354(6319): 7000.
Braenne I, Kleinecke M, Reiz B, et al. Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. Eur J Hum Genet 2015; 4: 1-7.
Bowen M, Kolor K, Dotson W, Ned R, Khoury M. Public health action in genomics is now needed beyond newborn screening. Pub Health Genom 2012; 15(6): 327-34.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 16 November, 2018
Page: [25 - 28]
Pages: 4
DOI: 10.2174/1570161116666180206111725
Price: $65

Article Metrics

PDF: 25