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Carotid Artery Atherosclerosis: A Review on Heritability and Genetics

  • Bianka Forgo (a1), Emanuela Medda (a2), Anita Hernyes (a1), Laszlo Szalontai (a1), David Laszlo Tarnoki (a1) and Adam Domonkos Tarnoki (a1)...


Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk, and therefore, assessing the genetic versus environmental background of CAS traits is of key importance. Carotid intima-media-thickness and plaque characteristics seem to be moderately heritable, with remarkable differences in both heritability and presence or severity of these traits among ethnicities. Although the considerable role of additive genetic effects is obvious, based on the results so far, there is an important emphasis on non-shared environmental factors as well. We aimed to collect and summarize the papers that investigate twin and family studies assessing the phenotypic variance attributable to genetic associations with CAS. Genes in relation to CAS markers were overviewed with a focus on genetic association studies and genome-wide association studies. Although the role of certain genes is confirmed by studies conducted on large populations and meta-analyses, many of them show conflicting results. A great focus should be on future studies elucidating the exact pathomechanism of these genes in CAS in order to imply them as novel therapeutic targets.


Corresponding author

address for correspondence: Adam Domonkos Tarnoki MD, PhD, Semmelweis University Department of Radiology, Üllői Street 78/A, Budapest 1082, Hungary. E-mail: tarnoki2@


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Abilleira, S., Bevan, S., & Markus, H. S. (2006). The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis. Journal of Medical Genetics, 43, 897901.
Aviram, M., & Vaya, J. (2013). Paraoxonase 1 activities, regulation, and interactions with atherosclerotic lesion. Current Opinion in Lipidology, 24, 339344.
Bella, J. N., Cole, S. A., Laston, S., Almasy, L., Comuzzie, A., Lee, E. T., . . . Goring, H. H. (2013). Genome-wide linkage analysis of carotid artery lumen diameter: The Strong Heart Family Study. International Journal of Cardiology, 168, 39023908.
Bijari, P. B., Wasserman, B. A., & Steinman, D. A. (2014). Carotid bifurcation geometry is an independent predictor of early wall thickening at the carotid bulb. Stroke, 45, 473478.
Bis, J. C., Kavousi, M., Franceschini, N., Isaacs, A., Abecasis, G. R., Schminke, U., . . . Consortium, C. A. (2011). Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nature Genetics, 43, 940947.
Bots, M. L., Hoes, A. W., Koudstaal, P. J., Hofman, A., & Grobbee, D. E. (1997). Common carotid intima-media thickness and risk of stroke and myocardial infarction: The Rotterdam Study. Circulation, 96, 14321437.
Breton, C. V., Wang, X., Mack, W. J., Berhane, K., Lopez, M., Islam, T. S., . . . Avol, E. (2011). Carotid artery intima-media thickness in college students: Race/ethnicity matters. Atherosclerosis, 217, 441446.
Cecelja, M., Jiang, B., Bevan, L., Frost, M. L., Spector, T. D., & Chowienczyk, P. J. (2011). Arterial stiffening relates to arterial calcification but not to noncalcified atheroma in women. A twin study. Journal of the American College of Cardiology, 57, 14801486.
Chambless, L. E., Folsom, A. R., Clegg, L. X., Sharrett, A. R., Shahar, E., Nieto, F. J., . . . Evans, G. (2000). Carotid wall thickness is predictive of incident clinical stroke: The Atherosclerosis Risk in Communities (ARIC) Study. American Journal Of Epidemiology, 151, 478487.
Chambless, L. E., Heiss, G., Folsom, A. R., Rosamond, W., Szklo, M., Sharrett, A. R., & Clegg, L. X. (1997). Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: The Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. American Journal of Epidemiology, 146, 483494.
Chapman, C. M., Beilby, J. P., Humphries, S. E., Palmer, L. J., Thompson, P. L., & Hung, J. (2003). Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population. European Heart Journal, 24, 14941499.
Chen, Y. C., Guo, X., Raffel, L. J., Xiang, A. H., Fang, B., Hsueh, W. A., . . . Rotter, J. I. (2008). Carotid intima-media thickness (cIMT) cosegregates with blood pressure and renal function in hypertensive Hispanic families. Atherosclerosis, 198, 160165.
Chien, K. L., Liau, C. S., Chen, M. F., Lee, Y. T., Jeng, J. S., Hwang, B. S., & Su, T. C. (2008). Primary hypercholesterolemia, carotid atherosclerosis and insulin resistance among Chinese. Lipids, 43, 117124.
Conde, L., Bevan, S., Sitzer, M., Klopp, N., Illig, T., Thiery, J., . . . Markus, H. S. (2011). Novel associations for coronary artery disease derived from genome wide association studies are not associated with increased carotid intima-media thickness, suggesting they do not act via early atherosclerosis or vessel remodeling. Atherosclerosis, 219 (2), 684689. doi:10.1016/j.atherosclerosis.2011.08.031
Cunnington, M. S., Mayosi, B. M., Hall, D. H., Avery, P. J., Farrall, M., Vickers, M. A., . . . Keavney, B. (2009). Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes. Atherosclerosis, 203, 4144.
den Hoed, M., Strawbridge, R. J., Almgren, P., Gustafsson, S., Axelsson, T., Engstrom, G., . . . Lind, L. (2015). GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb. Atherosclerosis, 239, 304310.
Djuric, T., Stankovic, A., Koncar, I., Radak, D., Davidovic, L., Alavantic, D., & Zivkovic, M. (2011). Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study. Atherosclerosis, 219, 673678.
Djuric, T., Zivkovic, M., Radak, D., Jekic, D., Radak, S., Stojkovic, L., . . . Alavantic, D. (2008). Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis. Clinical Biochemistry, 41, 13261329.
Dong, C., Beecham, A., Slifer, S., Wang, L., Blanton, S. H., Wright, C. B., . . . Sacco, R. L. (2010). Genomewide linkage and peakwide association analyses of carotid plaque in Caribbean Hispanics. Stroke, 41, 27502756.
Dronadula, N., Wacker, B. K., Van Der Kwast, R., Zhang, J., & Dichek, D. A. (2017). Stable in vivo transgene expression in endothelial cells with helper-dependent adenovirus: Roles of promoter and interleukin-10. Human Gene Therapy, 28, 255270.
Du, L., Dronadula, N., Tanaka, S., & Dichek, D. A. (2011). Helper-dependent adenoviral vector achieves prolonged, stable expression of interleukin-10 in rabbit carotid arteries but does not limit early atherogenesis. Human Gene Therapy, 22, 959968.
Duggirala, R., Gonzalez Villalpando, C., O'Leary, D. H., Stern, M. P., & Blangero, J. (1996). Genetic basis of variation in carotid artery wall thickness. Stroke, 27, 833837.
Durga, J., Verhoef, P., Bots, M. L., & Schouten, E. (2004). Homocysteine and carotid intima-media thickness: A critical appraisal of the evidence. Atherosclerosis, 176, 119.
Ebrahim, S., Papacosta, O., Whincup, P., Wannamethee, G., Walker, M., Nicolaides, A. N., . . . Lowe, G. D. (1999). Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: The British Regional Heart Study. Stroke, 30, 841850.
Fox, C. S., Polak, J. F., Chazaro, I., Cupples, A., Wolf, P. A., D'Agostino, R. A., . . . Framingham Heart, S. (2003). Genetic and environmental contributions to atherosclerosis phenotypes in men and women: Heritability of carotid intima-media thickness in the Framingham Heart Study. Stroke, 34, 397401.
Geisel, M. H., Coassin, S., Hessler, N., Bauer, M., Eisele, L., Erbel, R., . . . Kronenberg, F. (2016). Update of the effect estimates for common variants associated with carotid intima media thickness within four independent samples: The Bonn IMT Family Study, the Heinz Nixdorf Recall Study, the SAPHIR Study and the Bruneck Study. Atherosclerosis, 249, 8387.
Graham, I. M., Daly, L. E., Refsum, H. M., Robinson, K., Brattstrom, L. E., Ueland, P. M., . . . . Andria, G. (1997). Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. The Journal of the American Medical Association, 277, 17751781.
Haapanen, A., Koskenvuo, M., Kaprio, J., Kesaniemi, Y. A., & Heikkila, K. (1989). Carotid arteriosclerosis in identical twins discordant for cigarette smoking. Circulation, 80, 1016.
Heiskanen, M., Kahonen, M., Hurme, M., Lehtimaki, T., Mononen, N., Juonala, M., . . . Hulkkonen, J. (2010). Polymorphism in the IL10 promoter region and early markers of atherosclerosis: The cardiovascular risk in Young Finns Study. Atherosclerosis, 208, 190196.
Heiss, G., Sharrett, A. R., Barnes, R., Chambless, L. E., Szklo, M., & Alzola, C. (1991). Carotid atherosclerosis measured by B-mode ultrasound in populations: Associations with cardiovascular risk factors in the ARIC Study. American Journal Of Epidemiology, 134, 250256.
Hemerich, D., van der Laan, S. W., Tragante, V., den Ruijter, H. M., de Borst, G. J., Pasterkamp, G., . . . Asselbergs, F. W. (2015). Impact of carotid atherosclerosis loci on cardiovascular events. Atherosclerosis, 243, 466468.
Hernandez-Socorro, C. R., Rodriguez-Esparragon, F. J., Celli, J., & Lopez-Fernandez, J. C. (2017). Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants. Journal of the Neurological Sciences, 378, 146151.
Holdt, L. M., Beutner, F., Scholz, M., Gielen, S., Gabel, G., Bergert, H., . . . Teupser, D. (2010). ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 620627.
Holdt, L. M., Hoffmann, S., Sass, K., Langenberger, D., Scholz, M., Krohn, K., . . . Teupser, D. (2013). Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLOS Genetics, 9, e1003588.
Holdt, L. M., Sass, K., Gabel, G., Bergert, H., Thiery, J., & Teupser, D. (2011). Expression of Chr9p21 genes CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a)), p14(ARF)) and MTAP in human atherosclerotic plaque. Atherosclerosis, 214, 264270.
Holdt, L. M., Stahringer, A., Sass, K., Pichler, G., Kulak, N. A., Wilfert, W., . . . Teupser, D. (2016). Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nature Communications, 7, 12429.
Holdt, L. M., & Teupser, D. (2012). Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 196206.
Howard, G., Sharrett, A. R., Heiss, G., Evans, G. W., Chambless, L. E., Riley, W. A., & Burke, G. L. (1993). Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC investigators. Stroke, 24, 12971304.
Hu, W., Wei, R., Wang, L., Lu, J., Liu, H., & Zhang, W. (2018). Correlations of MMP-1, MMP-3, and MMP-12 with the degree of atherosclerosis, plaque stability and cardiovascular and cerebrovascular events. Experimental and Therapeutic Medicine, 15, 19941998.
Hu, X. F., Jin, X. P., Hu, P. Y., Zhu, M., Wang, F., Lin, X. F., . . . Yang, L. H. (2011). Association of a functional polymorphism in the MMP7 gene promoter with susceptibility to vulnerable carotid plaque in a Han Chinese population. Clinical Chemistry and Laboratory Medicine, 49, 17351741.
Hulkkonen, J., Lehtimaki, T., Mononen, N., Juonala, M., Hutri-Kahonen, N., Taittonen, L., . . . Kahonen, M. (2009). Polymorphism in the IL6 promoter region is associated with the risk factors and markers of subclinical atherosclerosis in men: The cardiovascular risk in Young Finns Study. Atherosclerosis, 203, 454458.
Humphries, S. E., & Morgan, L. (2004). Genetic risk factors for stroke and carotid atherosclerosis: Insights into pathophysiology from candidate gene approaches. Lancet Neurology, 3, 227235.
Hung, J., McQuillan, B. M., Nidorf, M., Thompson, P. L., & Beilby, J. P. (1999). Angiotensin-converting enzyme gene polymorphism and carotid wall thickening in a community population. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 19691974.
Hunt, K. J., Duggirala, R., Goring, H. H., Williams, J. T., Almasy, L., Blangero, J., . . . Stern, M. P. (2002). Genetic basis of variation in carotid artery plaque in the San Antonio Family Heart Study. Stroke, 33, 27752780.
Imbalzano, E., Vatrano, M., Quartuccio, S., Di Stefano, R., Aragona, C. O., Mamone, F., . . . Mandraffino, G. (2017). Clinical impact of angiotensin I converting enzyme polymorphisms in subjects with resistant hypertension. Molecular and Cellular Biochemistry, 430, 9198.
Jartti, L., Raitakari, O. T., Kaprio, J., Jarvisalo, M. J., Toikka, J. O., Marniemi, J., . . . Ronnemaa, T. (2002). Increased carotid intima-media thickness in men born in east Finland: A twin study of the effects of birthplace and migration to Sweden on subclinical atherosclerosis. Annals of Medicine, 34, 162170.
Jartti, L., Ronnemaa, T., Raitakari, O. T., Hedlund, E., Hammar, N., Lassila, R., . . . Kaprio, J. (2009). Migration at early age from a high to a lower coronary heart disease risk country lowers the risk of subclinical atherosclerosis in middle-aged men. Journal of Internal Medicine, 265, 345358.
Juo, S. H. (2009). Genetics of carotid atherosclerosis. Frontiers in Bioscience (Landmark edition), 14, 45254534.
Juo, S. H., Lin, H. F., Rundek, T., Sabala, E. A., Boden-Albala, B., Park, N., . . . Sacco, R. L. (2004). Genetic and environmental contributions to carotid intima-media thickness and obesity phenotypes in the Northern Manhattan Family Study. Stroke, 35, 22432247.
Juo, S. H., Rundek, T., Lin, H. F., Cheng, R., Lan, M. Y., Huang, J. S., . . . Sacco, R. L. (2005). Heritability of carotid artery distensibility in Hispanics: The Northern Manhattan Family Study. Stroke, 36, 2357–2361.
Kanters, S. D., Algra, A., van Leeuwen, M. S., & Banga, J. D. (1997). Reproducibility of in vivo carotid intima-media thickness measurements: A review. Stroke, 28, 665671.
Kao, W. H., Hsueh, W. C., Rainwater, D. L., O'Leary, D. H., Imumorin, I. G., Stern, M. P., & Mitchell, B. D. (2005). Family history of type 2 diabetes is associated with increased carotid artery intimal-medial thickness in Mexican Americans. Diabetes Care, 28, 18821889.
Kerwin, W. S., Hatsukami, T., Yuan, C., & Zhao, X. Q. (2013). MRI of carotid atherosclerosis. American Journal of Roentgenology, 200, W304–W313.
Kim, D. S., Li, Y. K., Bell, G. A., Burt, A. A., Vaisar, T., Hutchins, P. M., . . . Jarvik, G. P. (2016). Concentration of smaller high-density lipoprotein particle (HDL-P) is inversely correlated with carotid intima media thickening after confounder adjustment: The Multi Ethnic Study of Atherosclerosis (MESA). Journal of the American Heart Association, 5, e002977.
Kuipers, A. L., Kammerer, C. M., Miljkovic, I., Woodard, G. A., Bunker, C. H., Patrick, A. L., . . . Zmuda, J. M. (2013). Genetic epidemiology and genome-wide linkage analysis of carotid artery ultrasound traits in multigenerational African ancestry families. Atherosclerosis, 231, 120123.
Kuller, L. H., Shemanski, L., Psaty, B. M., Borhani, N. O., Gardin, J., Haan, M. N., . . . Tracy, R. (1995). Subclinical disease as an independent risk factor for cardiovascular disease. Circulation, 92, 720726.
Kulshreshtha, A., Goyal, A., Veledar, E., McClellan, W., Judd, S., Eufinger, S. C., . . . Vaccarino, V. (2014). Association between ideal cardiovascular health and carotid intima-media thickness: A twin study. Journal of the American Heart Association, 3, e000282.
Lange, L. A., Bowden, D. W., Langefeld, C. D., Wagenknecht, L. E., Carr, J. J., Rich, S. S., . . . Freedman, B. I. (2002). Heritability of carotid artery intima-medial thickness in type 2 diabetes. Stroke, 33, 18761881.
Lassila, R., Seyberth, H. W., Haapanen, A., Schweer, H., Koskenvuo, M., & Laustiola, K. E. (1988). Vasoactive and atherogenic effects of cigarette smoking: A study of monozygotic twins discordant for smoking. The British Medical Journal, 297, 955957.
Lee, K., Sung, J., Lee, S. C., Park, S. W., Kim, Y. S., Lee, J. Y., . . . Song, Y. M. (2012a). Segment-specific carotid intima-media thickness and cardiovascular risk factors in Koreans: The Healthy Twin Study. European Journal of Preventive Cardiology, 19, 11611172.
Lee, K., Sung, J., Lee, S. C., Park, S. W., Kim, Y. S., Lee, J. Y., & Song, Y. M. (2012b). Phenotypic and genetic relationships between kidney function and carotid intima-media thickness in Koreans: The Healthy Twin Study. Kidney and Blood Pressure Research, 35, 259264.
Li, C., Chen, W., Jiang, F., Simino, J., Srinivasan, S. R., Berenson, G. S., & Mei, H. (2015). Genetic association and gene-smoking interaction study of carotid intima-media thickness at five GWAS-indicated genes: The Bogalusa Heart Study. Gene, 562, 226231.
Li, C., Jin, X. P., Zhu, M., Chen, Q. L., Wang, F., Hu, X. F., . . . Zheng, Z. (2014). Positive association of MMP 14 gene polymorphism with vulnerable carotid plaque formation in a Han Chinese population. Scandinavian Journal of Clinical and Laboratory Investigation, 74, 248253.
Li, H., Kuipers, A., Kammerer, C. M., Bunker, C. H., Kuller, L. H., Miljkovic, I., . . . Zmuda, J. M. (2013). The association between renal function biomarkers and subclinical cardiovascular measures in African Caribbean families. Ethnicity & Disease, 23, 492498.
Li, Q., Huang, P., He, Q. C., Lin, Q. Z., Wu, J., & Yin, R. X. (2014). Association between the CETP polymorphisms and the risk of Alzheimer's disease, carotid atherosclerosis, longevity, and the efficacy of statin therapy. Neurobiology of Aging, 35, e1513–e1523.
Li, T. C., Li, C. I., Liao, L. N., Liu, C. S., Yang, C. W., Lin, C. H., . . . Lin, C. C. (2015). Associations of EDNRA and EDN1 polymorphisms with carotid intima media thickness through interactions with gender, regular exercise, and obesity in subjects in Taiwan: Taichung Community Health Study (TCHS). Biomedicine (Taipei), 5, 814.
Lioudaki, S., Verikokos, C., Kouraklis, G., Ioannou, C., Chatziioannou, E., Perrea, D., & Klonaris, C. (2017). Paraoxonase-1: Characteristics and role in atherosclerosis and carotid artery disease. Current Vascular Pharmacology, 20, 323334.
Litvinov, D., Mahini, H., & Garelnabi, M. (2012). Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases. North American Journal of Medicine & Science, 4, 523532.
Lopez-Mejias, R., Genre, F., Garcia-Bermudez, M., Ubilla, B., Castaneda, S., Llorca, J., . . . Gonzalez-Gay, M. A. (2014). Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and carotid intima-media thickness, carotid plaques, and cardiovascular disease in patients with rheumatoid arthritis. Mediators of Inflammation, 2014, 756279.
Lorenz, M. W., Markus, H. S., Bots, M. L., Rosvall, M., & Sitzer, M. (2007). Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation, 115, 459467.
Lucatelli, P., Fagnani, C., Tarnoki, A. D., Tarnoki, D. L., Sacconi, B., Fejer, B., . . . Medda, E. (2017). Genetic influence on femoral plaque and its relationship with carotid plaque: An international twin study. International Journal of Cardiovascular Imaging, 34, 531541.
Mackness, B., Durrington, P. N., & Mackness, M. I. (1998). Human serum paraoxonase. General Pharmacology, 31, 329336.
Mahdessian, H., Perisic Matic, L., Lengquist, M., Gertow, K., Sennblad, B., Baldassarre, D., . . . IMPROVE study group. (2017). Integrative studies implicate matrix metalloproteinase-12 as a culprit gene for large-artery atherosclerotic stroke. Journal of Internal Medicine, 282, 429444.
Markus, H., Kapozsta, Z., Ditrich, R., Wolfe, C., Ali, N., Powell, J., . . . Cullinane, M. (2001). Increased common carotid intima-media thickness in UK African Caribbeans and its relation to chronic inflammation and vascular candidate gene polymorphisms. Stroke, 32, 24652471.
Mayosi, B. M., Avery, P. J., Baker, M., Gaukrodger, N., Imrie, H., Green, F. R., . . . Keavney, B. (2005). Genotype at the -174G/C polymorphism of the interleukin-6 gene is associated with common carotid artery intimal-medial thickness: Family study and meta-analysis. Stroke, 36, 22152219.
Mazurek, K., Zmijewski, P., Czajkowska, A., & Lutoslawska, G. (2014). Gender differences in carotid artery intima-media thickness and flow-mediated dilatation in young, physically active adults. Journal of Sports Medicine and Physical Fitness, 54, 298306.
Medda, E., Fagnani, C., Schillaci, G., Tarnoki, A. D., Tarnoki, D. L., Baracchini, C., . . . Stazi, M. A. (2014). Heritability of arterial stiffness and carotid intima-media thickness: An Italian twin study. Nutrition, Metabolism & Cardiovascular Diseases, 24, 511517.
Melton, P. E., Carless, M. A., Curran, J. E., Dyer, T. D., Goring, H. H., Kent, J. W., . . . Almasy, L. (2013). Genetic architecture of carotid artery intima-media thickness in Mexican Americans. Circulation-Cardiovascular Genetics, 6, 211221.
Millwood, I. Y., Bennett, D. A., Holmes, M. V., Boxall, R., Guo, Y., Bian, Z., . . . China Kadoorie Biobank Collaborative, G. (2018). Association of CETP gene variants with risk for vascular and nonvascular diseases among Chinese adults. JAMA Cardiology, 3, 3443.
Miyaki, K. (2010). Genetic polymorphisms in homocysteine metabolism and response to folate intake: A comprehensive strategy to elucidate useful genetic information. Journal of Epidemiology, 20, 266270.
Moskau, S., Golla, A., Grothe, C., Boes, M., Pohl, C., & Klockgether, T. (2005). Heritability of carotid artery atherosclerotic lesions: An ultrasound study in 154 families. Stroke, 36, 58.
Naqvi, T. Z., & Lee, M. S. (2014). Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC: Cardiovascular Imaging, 7, 10251038.
Naqvi, T. Z., Mendoza, F., Rafii, F., Gransar, H., Guerra, M., Lepor, N., . . . Shah, P. K. (2010). High prevalence of ultrasound detected carotid atherosclerosis in subjects with low Framingham risk score: Potential implications for screening for subclinical atherosclerosis. Journal of the American Society of Echocardiography, 23, 809815.
Nikpay, M., Goel, A., Won, H. H., Hall, L. M., Willenborg, C., Kanoni, S., . . . Farrall, M. (2015). A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nature Genetics, 47, 11211130.
North, K. E., MacCluer, J. W., Devereux, R. B., Howard, B. V., Welty, T. K., Best, L. G., . . . Strong Heart Family Study. (2002). Heritability of carotid artery structure and function: The Strong Heart Family Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 22, 16981703.
Park, E. Y., Ahn, H. M., Lee, J. A., & Hong, Y. M. (2009). Insertion/deletion polymorphism of angiotensin converting enzyme gene in Korean hypertensive adolescents. Heart Vessels, 24, 193198.
Paternoster, L., Martinez-Gonzalez, N. A., Charleton, R., Chung, M., Lewis, S., & Sudlow, C. L. (2010). Genetic effects on carotid intima-media thickness: Systematic assessment and meta-analyses of candidate gene polymorphisms studied in more than 5000 subjects. Circulation. Cardiovascular Genetics, 3, 1521.
Pessi, T., Viiri, L. E., Raitoharju, E., Astola, N., Seppala, I., Waldenberger, M., . . . Monaco, C. (2015). Interleukin-6 and microRNA profiles induced by oral bacteria in human atheroma derived and healthy smooth muscle cells. Springerplus, 4, 206.
Phan, T. G., Beare, R. J., Jolley, D., Das, G., Ren, M., Wong, K., . . . Srikanth, V. (2012). Carotid artery anatomy and geometry as risk factors for carotid atherosclerotic disease. Stroke, 43, 15961601.
Pignoli, P., Tremoli, E., Poli, A., Oreste, P., & Paoletti, R. (1986). Intimal plus medial thickness of the arterial wall: A direct measurement with ultrasound imaging. Circulation, 74, 13991406.
Pleskovic, A., Letonja, M. S., Vujkovac, A. C., Starcevic, J. N., Caprnda, M., Curilla, E., . . . Petrovic, D. (2017). Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus. Vasa, 46, 363369.
Polak, J. F., Pencina, M. J., Pencina, K. M., O'Donnell, C. J., Wolf, P. A., & D'Agostino, R. B. (2011). Carotid-wall intima-media thickness and cardiovascular events. The New England Journal of Medicine, 365, 213221.
Polak, J. F., Person, S. D., Wei, G. S., Godreau, A., Jacobs, D. R., Harrington, A., . . . O'Leary, D. H. (2010). Segment-specific associations of carotid intima-media thickness with cardiovascular risk factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Stroke, 41, 915.
Pott, J., Burkhardt, R., Beutner, F., Horn, K., Teren, A., Kirsten, H., . . . Scholz, M. (2017). Genome-wide meta-analysis identifies novel loci of plaque burden in carotid artery. Atherosclerosis, 259, 3240.
Pramukarso, D. T., Faradz, S. M., Sari, S., & Hadisaputro, S. (2015). Association between methylenetetrahydrofolate reductase (MTHFR) polymorphism and carotid intima medial thickness progression in post ischaemic stroke patient. Annals of Translational Medicine, 3, 324.
Proust, C., Empana, J. P., Boutouyrie, P., Alivon, M., Challande, P., Danchin, N., . . . Lacolley, P. (2015). Contribution of rare and common genetic variants to plasma lipid levels and carotid stiffness and geometry: A substudy of the Paris Prospective Study 3. Circulation Cardiovascular Genetics, 8, 628636.
Rampersaud, E., Bielak, L. F., Parsa, A., Shen, H., Post, W., Ryan, K. A., . . . Mitchell, B. D. (2008). The association of coronary artery calcification and carotid artery intima-media thickness with distinct, traditional coronary artery disease risk factors in asymptomatic adults. American Journal of Epidemiology, 168, 10161023.
Rauramaa, R., Vaisanen, S. B., Luong, L. A., Schmidt-Trucksass, A., Penttila, I. M., Bouchard, C., . . . Humphries, S. E. (2000). Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 26572662.
Riikola, A., Sipila, K., Kahonen, M., Jula, A., Nieminen, M. S., Moilanen, L., . . . Hulkkonen, J. (2009). Interleukin-6 promoter polymorphism and cardiovascular risk factors: The Health 2000 Survey. Atherosclerosis, 207, 466470.
Rundek, T., Elkind, M. S., Pittman, J., Boden-Albala, B., Martin, S., Humphries, S. E., . . . Sacco, R. L. (2002). Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: The Northern Manhattan Prospective Cohort Study. Stroke, 33, 14201423.
Ryabikov, A., Malyutina, S., Ryabikov, M., Kuznetsova, T., Staessen, J. A., & Nikitin, Y. (2007). Intrafamilial correlations of carotid intima-media thickness and flow-mediated dilation in a Siberian population. American Journal of Hypertension, 20, 248254.
Ryder, J. R., Pankratz, N. D., Dengel, D. R., Pankow, J. S., Jacobs, D. R., Sinaiko, A. R., . . . Steinberger, J. (2017). Heritability of vascular structure and function: A Parent–Child Study. Journal of the American Heart Association, 6, e004757.
Sacco, R. L., Blanton, S. H., Slifer, S., Beecham, A., Glover, K., Gardener, H., . . . Rundek, T. (2009). Heritability and linkage analysis for carotid intima-media thickness: The family study of stroke risk and carotid atherosclerosis. Stroke, 40, 23072312.
Salonen, J. T., & Salonen, R. (1991). Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arteriosclerosis and Thrombosis, 11, 12451249.
Sayed-Tabatabaei, F. A., Houwing-Duistermaat, J. J., van Duijn, C. M., & Witteman, J. C. (2003). Angiotensin-converting enzyme gene polymorphism and carotid artery wall thickness: A meta-analysis. Stroke, 34, 16341639.
Sayed-Tabatabaei, F. A., van Rijn, M. J., Schut, A. F., Aulchenko, Y. S., Croes, E. A., Zillikens, M. C., . . . van Duijn, C. M. (2005). Heritability of the function and structure of the arterial wall: Findings of the Erasmus Rucphen Family (ERF) Study. Stroke, 36, 23512356.
Shendre, A., Irvin, M. R., Aouizerat, B. E., Wiener, H. W., Vazquez, A. I., Anastos, K., . . . Shrestha, S. (2014). RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS). Atherosclerosis, 233, 666672.
Shendre, A., Wiener, H. W., Irvin, M. R., Aouizerat, B. E., Overton, E. T., Lazar, J., . . . Shrestha, S. (2017). Genome-wide admixture and association study of subclinical atherosclerosis in the Women's Interagency HIV Study (WIHS). PLoS One, 12, e0188725.
Shrestha, S., Irvin, M. R., Taylor, K. D., Wiener, H. W., Pajewski, N. M., Haritunians, T., . . . Grunfeld, C. (2010). A genome-wide association study of carotid atherosclerosis in HIV-infected men. Journal of Acquired Immune Deficiency Syndromes, 24, 583592.
Singh, A., Babyak, M. A., Nolan, D. K., Brummett, B. H., Jiang, R., Siegler, I. C., . . . Hauser, E. R. (2015). Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene. European Journal of Human Genetics, 23, 854862.
Song, Y. M., Lee, K., Sung, J., Kim, Y. S., & Lee, J. Y. (2012). Sex-specific relationships between adiposity and anthropometric measures and carotid intima-media thickness in Koreans: The Healthy Twin Study. European Journal of Clinical Nutrition, 66, 3946.
Stein, J. H., Korcarz, C. E., Hurst, R. T., Lonn, E., Kendall, C. B., Mohler, E. R., . . . American Society of Echocardiography Carotid Intima-Media Thickness Task, F. (2008). Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force. endorsed by the society for vascular medicine. Journal of the American Society of Echocardiography, 21, 93111, quiz 189–190.
Sun, K., Song, J., Liu, K., Fang, K., Wang, L., Wang, X., . . . Hu, Y. (2017). Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: A Chinese sib pair study. Journal of Thrombosis and Thrombolysis, 43, 401410.
Susser, M., & Susser, E. (1987). Indicators and designs in genetic epidemiology: Separating heredity and environment. Revue d'Epidémiologie et de Santé Publique, 35, 5477.
Swan, L., Birnie, D. H., Inglis, G., Connell, J. M., & Hillis, W. S. (2003). The determination of carotid intima medial thickness in adults – A population-based twin study. Atherosclerosis, 166, 137141.
Tarnoki, A. D., Baracchini, C., Tarnoki, D. L., Lucatelli, P., Boatta, E., Zini, C., . . . Schillaci, G. (2012). Evidence for a strong genetic influence on carotid plaque characteristics: An international twin study. Stroke, 43, 31683172.
Tsai, M. Y., Johnson, C., Kao, W. H., Sharrett, A. R., Arends, V. L., Kronmal, R., . . . Post, W. (2008). Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the multi-ethnic study of atherosclerosis. Atherosclerosis, 200, 359367.
van der Meer, I. M., Bots, M. L., Hofman, A., del Sol, A. I., van der Kuip, D. A., & Witteman, J. C. (2004). Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: The Rotterdam Study. Circulation, 109, 10891094.
Vargas, J. D., Manichaikul, A., Wang, X. Q., Rich, S. S., Rotter, J. I., Post, W. S., . . . Bluemke, D. A. (2016). Common genetic variants and subclinical atherosclerosis: The multi-ethnic study of atherosclerosis (MESA). Atherosclerosis, 245, 230236.
Wang, D., Yang, H., Quinones, M. J., Bulnes-Enriquez, I., Jimenez, X., De La Rosa, R., . . . Rotter, J. I. (2005). A genome-wide scan for carotid artery intima-media thickness: The Mexican-American coronary artery disease family study. Stroke, 36, 540545.
Wang, F., Jin, X. P., Zhu, M., Lin, X. F., Hu, X. F., Wang, W. F., . . . Huang, L. Z. (2011). Genotype association of C(-735)T polymorphism of the MMP-2 gene with the risk of carotid atherosclerosis-vulnerable plaque in the Han Chinese population. Vascular Medicine, 16, 1318.
Wasserman, B. A., Astor, B. C., Sharrett, A. R., Swingen, C., & Catellier, D. (2010). MRI measurements of carotid plaque in the Atherosclerosis Risk in Communities (ARIC) Study: Methods, reliability and descriptive statistics. Journal of Magnetic Resonance Imaging, 31, 406415.
Whincup, P. H., Nightingale, C. M., Owen, C. G., Rapala, A., Bhowruth, D. J., Prescott, M. H., . . . Deanfield, J. E. (2012). Ethnic differences in carotid intima-media thickness between UK children of black African-Caribbean and white European origin. Stroke, 43, 17471754.
Wikstrand, J. (2007). Methodological considerations of ultrasound measurement of carotid artery intima-media thickness and lumen diameter. Clinical Physiology and Functional Imaging, 27, 341345.
Wilkening, S., Chen, B., Bermejo, J. L., & Canzian, F. (2009). Is there still a need for candidate gene approaches in the era of genome-wide association studies? Genomics, 93, 415419.
Woessner, J. F. (1991). Matrix metalloproteinases and their inhibitors in connective-tissue remodeling. FASEB Journal, 5, 21452154.
Wong, M., Edelstein, J., Wollman, J., & Bond, M. G. (1993). Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arteriosclerosis, Thrombosis, and Vascular Biology, 13, 482486.
World Health Organization. (2017). Cardiovascular disease. Retrieved from
Xiang, A. H., Azen, S. P., Buchanan, T. A., Raffel, L. J., Tan, S., Cheng, L. S., . . . Hodis, H. N. (2002). Heritability of subclinical atherosclerosis in Latino families ascertained through a hypertensive parent. Arteriosclerosis, Thrombosis, and Vascular Biology, 22, 843848.
Xie, G., Myint, P. K., Voora, D., Laskowitz, D. T., Shi, P., Ren, F., . . . Wu, Y. (2015). Genome-wide association study on progression of carotid artery intima media thickness over 10 years in a Chinese cohort. Atherosclerosis, 243, 3037.
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011). GCTA: A tool for genome-wide complex trait analysis. American Journal of Human Genetics, 88, 7682.
Ye, S., Eriksson, P., Hamsten, A., Kurkinen, M., Humphries, S. E., & Henney, A. M. (1996). Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. Journal of Biological Chemistry, 271, 1305513060.
Yu, G. I., Jun, S. E., Cho, H. C., Park, K. O., Chung, J. H., Shin, D. H., & Chung, I. S. (2015). Association of interleukin-10 promoter region polymorphisms with risk factors of Atherosclerosis. International Journal of Immunogenetics, 42, 3137.
Zhang, Y., Wang, L., Zhang, Z., Zhang, Z., Zhou, S., Cao, L., . . . Xu, G. (2015). Shared and discrepant susceptibility for carotid artery and aortic arch calcification: A genetic association study. Atherosclerosis, 241, 371375.
Zhao, C., Ikeda, S., Arai, T., Naka-Mieno, M., Sato, N., Muramatsu, M., & Sawabe, M. (2014). Association of the RYR3 gene polymorphisms with atherosclerosis in elderly Japanese population. BMC Cardiovascular Disorders, 14, 6.
Zhao, J., Cheema, F. A., Bremner, J. D., Goldberg, J., Su, S., Snieder, H., . . . Vaccarino, V. (2008). Heritability of carotid intima-media thickness: A twin study. Atherosclerosis, 197, 814820.
Zhi, D., Shendre, A., Scherzer, R., Irvin, M. R., Perry, R. T., Levy, S., . . . Shrestha, S. (2015). Deep sequencing of RYR3 gene identifies rare and common variants associated with increased carotid intima-media thickness (CIMT) in HIV-infected individuals. Journal of Human Genetics, 60, 6367.
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Twin Research and Human Genetics
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  • EISSN: 1839-2628
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