New advances in identifying genetic anomalies in stroke-prone probands
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.
- Joutel A, Corpechot C, Ducros A, et al.: Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996, 383:707–710. CrossRef
- Gretarsdottir S, Sveinbjornsdottir S, Jonsson HH, et al.: Localization of a susceptibility gene for common forms of stroke to 5q12. Am J Hum Genet 2002, 70:593–603. This is the first genome-wide scan for stroke risk factors in humans. Using a unique database that includes genetic, genealogic, and medical information on nearly everyone in Iceland, investigators identified a stroke risk factor locus on chromosome 5q12 designated STRK1. CrossRef
- Meschia JF, Brown RD Jr, Brott TG, et al.: The Siblings With Ischemic Stroke Study (SWISS) Protocol. BMC Med Genet 2002, 3:1. This is an ongoing, 50-center study that assembles informative ischemic stroke pedigrees using a decentralized recruitment of probands and centralized recruitment of stroke-affected and stroke-unaffected siblings. Its goal is to conduct a second genomewide linkage study for stroke risk factor loci. CrossRef
- Worrall BB, Chen DT, Meschia JF: Ethical and methodological issues in pedigree stroke research. Stroke 2001, 32:1242–1249.
- Markus HS, Martin RJ, Simpson MA, et al.: Diagnostic strategies in CADASIL. Neurology 2002, 59:1134–1138. Investigators studied 83 potential index cases of CADASIL in Britain. Granular osmophilic material on skin biopsy was diagnostic of the condition, and anterior temporal pole involvement on brain magnetic resonance imaging was useful as a diagnostic marker.
- Joutel A, Dodick DD, Parisi JE, et al.: De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol 2000, 47:388–391. CrossRef
- Joutel A, Favrole P, Labauge P, et al.: Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001, 358:2049–2051. Immunostaining of skin biopsy specimens with an anti-notch 3 antibody was found to have a sensitivity of 96% and specificity of 100% for diagnosing CADASIL in a retrospective series of 39 patients. CrossRef
- Dichgans M, Holtmannspotter M, Herzog J, et al.: Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke 2002, 33:67–71. CrossRef
- Hancock DK, Schwarz FP, Song F, et al.: Design and use of a peptide nucleic acid for detection of the heteroplasmic low-frequency mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) mutation in human mitochondrial DNA. Clin Chem 2002, 48:2155–2163. Investigators developed a highly sensitive assay for the MELAS A3243G mutation using peptide nucleic acids.
- Schwartz M, Vissing J: Paternal inheritance of mitochondrial DNA. N Engl J Med 2002, 347:576–580. CrossRef
- Adams RJ, McKie VC, Brambilla D, et al.: Stroke prevention trial in sickle cell anemia. Control Clin Trial 1998, 19:110–129. CrossRef
- Sarnaik SA, Ballas SK: Molecular characteristics of pediatric patients with sickle cell anemia and stroke. Am J Hematol 2001, 67:179–182. CrossRef
- Taylor VI, Tang DC, Savage SA, et al.: Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood 2002, 100:4303–4309. CrossRef
- Tang DC, Prauner R, Liu W, et al.: Polymorphisms within the angiotensinogen gene (GT-repeat) and the risk of stroke in pediatric patients with sickle cell disease: a case-control study. Am J Hematol 2001, 68:164–169. CrossRef
- Stensland-Bugge E, Bonaa KH, Joakimsen O: Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromso study. Atherosclerosis 2001, 154:437–448. CrossRef
- Zannad F, Visvikis S, Gueguen R, et al.: Genetics strongly determines the wall thickness of the left and right carotid arteries. Hum Genet 1998, 103:183–188. CrossRef
- Visvikis S, Sass C, Pallaud C, et al.: Familial studies on the genetics of cardiovascular diseases: the Stanislas cohort. Clin Chem Lab Med 2000, 38:827–832. CrossRef
- North KE, MacCluer JW, Devereux RB, et al.: Heritability of carotid artery structure and function: the Strong Heart Family Study. Arterioscler Thromb Vasc Biol 2002, 22:1698–1703. CrossRef
- Lange LA, Bowden DW, Langefeld CD, et al.: Heritability of carotid artery intima-medial thickness in type 2 diabetes. Stroke 2002, 33:1876–1881. CrossRef
- Rundek T, Elkind MS, Pittman J, et al.: 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 2002, 33:1420–1423. CrossRef
- Homma S, Hirose N, Ishida H, et al.: Carotid plaque and intima-media thickness assessed by B-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke 2001, 32:830–835.
- Balkestein EJ, Wang JG, Struijker-Boudier HA, et al.: Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population. J Hypertens 2002, 20:1551–1561. CrossRef
- Diamantopoulos EJ, Andreadis E, Kakou M, et al.: Atherosclerosis of carotid arteries and the ACE insertion/deletion polymorphism in subjects with diabetes mellitus type 2. Int Angiol 2002, 21:63–69.
- Kelly PJ, Rosand J, Kistler JP, et al.: Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 2002, 59:529–536. This meta-analysis confirms that hyperhomocysteinemia is a risk factor for stroke. The evidence for the MTHFR TT genotype being a risk factor for stroke was not compelling.
- Homocysteine Studies Collaboration: Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002, 288:2015–2022. CrossRef
- Conroy JM, Trivedi G, Sovd T, Caggana M: The allele frequency of mutations in four genes that confer enhanced susceptibility to venous thromboembolism in an unselected group of New York State newborns. Thromb Res 2000, 99:317–324. CrossRef
- Wald DS, Law M, Morris JK: Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002, 325:1202. CrossRef
- Szolnoki Z, Somogyvari F, Kondacs A, et al.: Evaluation of the interactions of common genetic mutations in stroke subtypes. J Neurol 2002, 249:1391–1397. CrossRef
- Haraki T, Takegoshi T, Kitoh C, et al.: Carotid artery intimamedia thickness and brachial artery flow-mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes. J Intern Med 2002, 252:114–120. CrossRef
- DeCarli C, Reed T, Miller BL, et al.: Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study. Stroke 1999, 30:1548–1553.
- Faggin E, Zambon A, Puato M, et al.: Association between the --514 C-->T polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis. J Am Coll Cardiol 2002, 40:1059–1066. CrossRef
- Shimo-Nakanishi Y, Urabe T, Hattori N, et al.: Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke 2001, 32:1481–1486.
- Nicklin MJ, Hughes DE, Barton JL, et al.: Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med 2000, 191:303–312. CrossRef
- Dewberry R, Holden H, Crossman D, Francis S: Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler Thromb Vasc Biol 2000, 20:2394–2400.
- Worrall BB, Azhar S, Nyquist PA, et al.: Interleukin-1 receptor antagonist gene polymorphisms in carotid atherosclerosis. Stroke 2003, 34:790–793. CrossRef
- Mackness B, Mackness MI, Arrol S, et al.: Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 1998, 423:57–60. CrossRef
- Voetsch B, Benke KS, Damasceno BP, et al.: Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002, 33:1459–1464. CrossRef
- Zuliani G, Cherubini A, Volpato S, et al.: Genetic factors associated with the absence of atherosclerosis in octogenarians. J Gerontol A Biol Sci Med Sci 2002, 57:M611–615.
- Allebrandt KV, Souza RL, Chautard-Freire-Maia EA: Variability of the paraoxonase gene (PON1) in Euro-and Afro-Brazilians. Toxicol Appl Pharmacol 2002, 180:151–156. CrossRef
- Senti M, Aubo C, Tomas M: Differential effects of smoking on myocardial infarction risk according to the Gln/Arg 192 variants of the human paraoxonase gene. Metabolism 2000, 49:557–559. CrossRef
- Chen Q, Reis SE, Kammerer CM, et al.: Association between the severity of angiographic coronary artery disease and paraoxonase gene polymorphisms in the National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study. Am J Hum Genet 2003, 72:13–22. CrossRef
- Xu XH, Shah PK, Faure E, et al.: Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation 2001, 104:3103–3108.
- Kiechl S, Lorenz E, Reindl M, et al.: Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002, 347:185–192. CrossRef
- Ezekowitz RA: Genetic heterogeneity of mannose-binding proteins: the Jekyll and Hyde of innate immunity? Am J Hum Genet 1998, 62:6–9. CrossRef
- Hegele RA, Ban MR, Anderson CM, Spence JD: Infectionsusceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area. J Invest Med 2000, 48:198–202.
- Rugonfalvi-Kiss S, Endresz V, Madsen HO, et al.: Association of Chlamydia pneumoniae with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation 2002, 106:1071–1076. CrossRef
- Sierra C, Coca A, Gomez-Angelats E, et al.: Renin-angiotensin system genetic polymorphisms and cerebral white matter lesions in essential hypertension. Hypertension 2002, 39:343–347. CrossRef
- Hassan A, Lansbury A, Catto AJ, et al.: Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes. J Neurol Neurosurg Psychiatry 2002, 72:343–346. CrossRef
- Zee RY, Ridker PM, Stampfer MJ, et al.: Prospective evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of stroke. Circulation 1999, 99:340–343.
- Doi Y, Yoshinari M, Yoshizumi H, et al.: Polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with thrombotic brain infarction. Atherosclerosis 1997, 132:145–150. CrossRef
- Hooper WC, Lally C, Austin H, et al.: The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans. Chest 1999, 116:880–886. CrossRef
- Hou L, Osei-Hyiaman D, Yu H, et al.: Association of a 27-bp repeat polymorphism in ecNOS gene with ischemic stroke in Chinese patients. Neurology 2001, 56:490–496.
- Yahashi Y, Kario K, Shimada K, Matsuo M: The 27-bp repeat polymorphism in intron 4 of the endothelial cell nitric oxide synthase gene and ischemic stroke in a Japanese population. Blood Coagul Fibrinolysis 1998, 9:405–409.
- Elbaz A, Poirier O, Moulin T, et al.: Association between the Glu298Asp polymorphism in the endothelial constitutive nitric oxide synthase gene and brain infarction. The GENIC Investigators. Stroke 2000, 31:1634–1639.
- Kim JS, Choi-Kwon S: Risk factors for stroke in different levels of cerebral arterial disease. Eur Neurol 1999, 42:150–156. CrossRef
- Karvonen J, Kauma H, Kervinen K, et al.: Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort. J Intern Med 2002, 251:102–110. CrossRef
- Lembo G, De Luca N, Battagli C, et al.: A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis. Stroke 2001, 32:735–740.
- Ghilardi G, Biondi ML, DeMonti M, et al.: Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosis. Stroke 2002, 33:2408–2412. CrossRef
- Rauramaa R, Vaisanen SB, Luong LA, et al.: Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Arterioscler Thromb Vasc Biol 2000, 20:2657–2662.
- Psaty BM, Smith NL, Heckbert SR, et al.: Diuretic therapy, the alpha-adducin gene variant, and the risk of myocardial infarction or stroke in persons with treated hypertension. JAMA 2002, 287:1680–1689. combined risk of stroke and myocardial infarction was lower with diuretic therapy versus other antihypertensive therapy in patients who were carriers of the Trp460 variant of the adducin gene. Genetics may cause medicine to move beyond the current "one-size-fits-all" approach to treating hypertension. CrossRef
- Rosskopf D, Manthey I, Siffert W: Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. Pharmacogenetics 2002, 12:209–220. CrossRef
- Wenzel RR, Siffert W, Bruck H, et al.: Enhanced vasoconstriction to endothelin-1, angiotensin II and noradrenaline in carriers of the GNB3 825T allele in the skin microcirculation. Pharmacogenetics 2002, 12:489–495. CrossRef
- Turner ST, Schwartz GL, Chapman AB, Boerwinkle E: C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic. Hypertension 2001, 37:739–743.
- Muckian C, Fitzgerald A, O’Neill A, et al.: Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: association of type III collagen COL3A1 polymorphisms with coronary artery disease. Blood 2002, 100:1220–1223. CrossRef
- New advances in identifying genetic anomalies in stroke-prone probands
Current Neurology and Neuroscience Reports
Volume 4, Issue 5 , pp 420-426
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links