Meta-analysis of genetic studies in ischemic stroke: Thirty-two genes involving approximately 18 000 cases and 58 000 controls

Archives of Neurology

Volumn 61, Issue 11, 2004, Pages 1652-1661

  Casas, Juan P ^a   Hingorani, Aroon D ^a   Bautista, Leonelo E ^b   Sharma, Pankaj ^c,d  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); APOLIPOPROTEIN E; BLOOD CLOTTING FACTOR 13; BLOOD CLOTTING FACTOR 5; DIPEPTIDYL CARBOXYPEPTIDASE; GLYCOPROTEIN IIIA; PROTHROMBIN;

CASE CONTROL STUDY; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; DNA POLYMORPHISM; EMBASE; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; HUMAN; MEDLINE; META ANALYSIS; PRIORITY JOURNAL; REVIEW; RISK FACTOR;

BRAIN ISCHEMIA; CASE-CONTROL STUDIES; CEREBROVASCULAR ACCIDENT; DATABASES, FACTUAL; GENETIC PREDISPOSITION TO DISEASE; HUMANS; RISK FACTORS;

EID: 7744222619     PISSN: 00039942     EISSN: None     Source Type: Journal    
DOI: 10.1001/archneur.61.11.1652     Document Type: Review

References (131)

1. World Health Organization. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organization; 2002.
2. National Heart, Lung, and Blood Institute. Morbidity & Mortality: 2002 Chartbook on Cardiovascular, Lung, and Blood Diseases. Bethesda, Md: National Institutes of Health; 2002.
3. American Heart Association. Economic cost of cardiovascular diseases. Available at: http://www.americanheart.org/statistics/10econom.html. Accessed June 15, 2003.
4. Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation. 2001;103:163-182.
5. Hrubec Z, Robinette CD. The study of human twins in medical research. N Engl J Med. 1984;310:435-441.
6. Brass LM, Isaacsohn JL, Merikangas KR, et al. A study of twins and stroke. Stroke. 1992;23:221-223.
7. Rubattu S, Volpe M, Kreutz R, Ganten U, Ganten D, Lindpaintner K. Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease. Nat Genet. 1996;13:429-434.
8. Kiely DK, Wolf PA, Cupples LA, et al. Familial aggregation of stroke: the Framingham Study. Stroke. 1993;24:1366-1371.
9. Sharma P. Genes for ischaemic stroke: strategies for their detection. J Hypertens. 1996;14:277-285.
10. Liao D, Myers R, Hunt S, et al. Familial history of stroke and stroke risk: the Family Heart Study. Stroke. 1997;28:1908-1912.
11. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719-748.
12. Robins J, Greenland S, Breslow NE. A general estimator of the variance of the Mantel-Haenszel odds ratio. Am J Epidemiol. 1986;124:719-723.
13. DerSimonian R, Laird NM. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188.
14. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in a meta-analysis. In: Egger M, Davey Smith G, Altman DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. Annapolis Junction, Md: BMJ Publishing Group; 2001.
15. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629-634.
16. Albucher JF, Guiraud-Chaumeil B, Chollet F, Cadroy Y, Sie P. Frequency of resistance to activated protein C due to factor V mutation in young patients with ischemic stroke. Stroke. 1996;27:766-767.
17. Bentolila S, Ripoll L, Drouet L, Mazoyer E, Woimant F. Thrombophilia due to 20210 G→A prothrombin polymorphism and cerebral ischemia in the young. Stroke. 1997;28:1846-1847.
18. Catto A, Carter A, Ireland H, et al. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol. 1995;15:783-785.
19. Chimowitz M, Mansbach H, Schmaier A, Nichols W, Ginsburg D. Factor V mutation and cryptogenic stroke in the young [abstract]. Stroke. 1996;27:188.
20. De Stefano V, Chiusolo P, Paciaroni K, et al. Prothrombin G20210A mutant geno-type is a risk factor for cerebrovascular ischemic disease in young patients. Blood. 1998;91:3562-3565.
21. Halbmayer WM, Haushofer A, Angerer V, Finsterer J, Fischer M; Vienna Thrombophilia in Stroke Study Group (VITISS). APC resistance and factor V Leiden (FV:Q506) mutation in patients with ischemic cerebral events. Blood Coagul Fibrinolysis. 1997;8:361-364.
22. Hankey GJ, Eikelboom JW, van Bockxmeer FM, Lofthouse E, Staples N, Baker RI. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke. 2001;32:1793-1799.
23. Iniesta JA, Corral J, Gonzalez-Conejero R, Rivera J, Vicente V. Prothrombotio genetic risk factors in patients with coexisting migraine and ischemic cerebrovascular disease. Headache. 1999;39:486-489.
24. Juul K, Tybjaerg-Hansen A, Steffensen R, Kofoed S, Jensen G, Nordestgaard BG. Factor V Leiden: the Copenhagen City Heart Study and 2 meta-analyses. Blood. 2002;100:3-10.
25. Kontula K, Ylikorkala A, Miettinen H, et al. Arg506Gln factor V mutation (factor V Leiden) in patients with ischaemic cerebrovascular disease and survivors of myocardial infarction. Thromb Haemost 1995;73:558-560.
26. Lalouschek W, Aull S, Series W, Zeiler K, Mannhalter C. The prothrombin G20210A mutation and factor V Leiden mutation in patients with cerebrovascular disease [letter]. Blood. 1998;92:704-705.
27. Landi G, Cella E, Martinelli I, Tagliabue L, Mannucci PM, Zerbi D. Arg506Gln factor V mutation and cerebral ischemia in the young [letter]. Stroke. 1996;27:1697-1698.
28. Lopaciuk S, Bykowska K, Kwiecinski H, et al. Factor V Leiden, prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase C677T genotype in young adults with ischemic stroke. Clin Appl Thromb Hemost. 2001;7:346-350.
29. Madonna P, de Stefano V, Coppola A, et al. Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke. Stroke. 2002;33:51-56.
30. Margaglione M, D'Andrea G, Giuliani N, et al. Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden. Arterioscler Thromb Vasc Biol. 1999;19:1751-1756.
31. Markus HS, Zhang Y, Jeffery S. Screening for the factor-V Arg 506 Gln mutation in patients with TIA and stroke. Cerebrovasc Dis. 1996;6:360-362.
32. Martinelli I, Franchi F, Akwan S, Bettini P, Merati G, Mannucci PM. The transition G to A at position 20210 in the 3′-untranslated region of the prothrombin gene is not associated with cerebral ischemia [letter]. Blood. 1997;90:3806.
33. Nabavi DG, Junker R, Wolff E, et al. Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients. J Neurol. 1998;245:653-658.
34. Pezzini A, Del Zotto E, Magoni M, et al. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke. 2003;34:28-33.
35. Press RD, Liu XY, Beamer N, Coull BM. Ischemic stroke in the elderly; role of the common factor V mutation causing resistance to activated protein C. Stroke. 1996;27:44-48.
36. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. 1995;332:912-917.
37. Sanchez J, Roman J, de la Torre MJ, Velasco F, Torres A. Low prevalence of the factor V Leiden among patients with ischemic stroke. Haemostasis. 1997;27:9-15.
38. Szolnoki Z, Somogyvari F, Kondacs A, Szabo M, Fodor L. Evaluation of the interactions of common genetic mutations in stroke subtypes. J Neurol. 2002;249:1391-1397.
39. van der Bom JG, Bots ML, Haverkate F, et al. Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med. 1996;125:265-269.
40. Voetsch B, Damasceno BP, Camargo EC, et al. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults. Thromb Haemost 2000;83:229-233.
41. Zunker P, Hohenstein C, Plendl HJ, et al. Activated protein C resistance and acute ischaemic stroke: relation to stroke causation and age. J Neurol. 2001;248:701-704.
42. Duca F, Sacchi E, Tagliabue L, Tajoli E. C677T methylenetetrahydrofolate reductase (MTHFR) mutation in stroke [abstract]. Thromb Haemost. 1997;78(suppl):102.
43. Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI. Association between high homocysteine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke. 2000;31:1069-1075.
44. Gross B, Antebi A, Cassel A, Honigman S. Is a mutation in the enzyme MTHFR a risk factor for stroke in young adults [abstract]? Neurology. 2000;54(suppl 3):A142.
45. Harmon DL, Doyle RM, Meleady R, et al. Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. Arterioscler Thromb Vasc Biol. 1999;19:208-211.
46. Kostulas K, Crisby M, Huang WX, et al. A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and in carotid artery stenosis. Eur J Clin Invest. 1998;28:285-289.
47. Kristensen B, Malm J, Nilsson TK, et al. Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke. Stroke. 1999;30:974-980.
48. Lalouschek W, Aull S, Serles W, et al. Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischemic cerebrovascular disease and in healthy control subjects. J Lab Clin Med. 1999;133:575-582.
49. Markus HS, Ali N, Swaminathan R, Sankaralingam A, Molloy J, Powell J. A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke. 1997;28:1739-1743.
50. McIlroy SP, Dynan KB, Lawson JT, Patterson CC, Passmore AP. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke. 2002;33:2351-2356.
51. Pezzini A, Del Zotto E, Archetti S, et al. Plasma homocysteine concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype in young adults with spontaneous cervical artery dissection and atherothrombotic stroke. Stroke. 2002;33:664-669.
52. Press RD, Beamer N, Evans A, DeLoughery TG, Coull BM. Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke. Diagn Mol Pathol. 1999;8:54-58.
53. Reuner KH, Ruf A, Kaps M, Druschky KF, Patscheke H. The mutation C677→T in the methylene tetrahydrofolate reductase gene and stroke. Thromb Haemost. 1998;79:450-451.
54. Salooja N, Catto A, Carter A, Tudenham EG, Grant PJ. Methylene tetrahydrofolate reductase C677T genotype and stroke. Clin Lab Haematol. 1998;20:357-361.
55. Soriente L, Coppola A, Madonna P, et al. Homozygous C677T mutation of the 5,10 methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in Italian patients with a history of early-onset ischemic stroke. Stroke. 1998;29:869-871.
56. Topic E, Timundic AM, Ttefanovic M, et al. Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab Med. 2001;39:346-350.
57. Egan RA, Kuyl JM, Press R, Lutsep HL. Lack of prothrombin gene mutation in young stroke patients. J Stroke Cerebrovasc Dis. 2000;9:229-231.
58. Gomez Garcia EB, van Goor MP, Leebeek FW, Brouwers GJ, Koudstaal PJ, Dippel DW. Elevated prothrombin is a risk factor for cerebral arterial ischemia in young adults. Clin Neurol Neurosurg. 2002;104:285-288.
59. Halbmayer WM, Haushofer A, Hermann KM, Fischer M. The 20210A allele of the prothrombin gene: a risk factor for juvenile stroke? result of a pilot study [letter]. Blood Coagul Fibrinolysis. 1998;9:209-210.
60. Lichy C, Reuner KH, Buggle F, et al. Prothrombin g20210a mutation, but not factor V Leiden, is a risk factor in patients with cerebral ischemia associated with persistent foramen ovale. Paper presented at: 16th International Congress on Fibrinolysis and Proteolysis in conjunction with the 17th International Fibrinogen Workshop; September 8-13, 2002; Munich, Germany.
61. Reuner KH, Ruf A, Grau A, et al. Prothrombin gene G20210→A transition is a risk factor for cerebral venous thrombosis. Stroke. 1998;29:1765-1769.
62. Ridker PM, Hennekens CH, Miletich JP. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation. 1999;99:999-1004.
63. Smiles AM, Jenny NS, Tang Z, Arnold A, Cushman M, Tracy RP. No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. Thromb Haemost. 2002;87:614-621.
64. Agerholm-Larsen B, Tybjaerg-Hansen A, Frikke-Schmidt R, Gronholdt ML, Jensen G, Nordestgaard BG. ACE gene polymorphism as a risk factor for ischemic cerebrovascular disease. Ann Intern Med. 1997;127:346-355.
65. Catto A, Carter AM, Barrett JH, et al. Angiotensin-converting enzyme insertion/ deletion polymorphism and cerebrovascular disease. Stroke. 1996;27:435-440.
66. Kostulas K, Huang WX, Crisby M, et al. An angiotensin-converting enzyme gene polymorphism suggests a genetic distinction between ischaemic stroke and carotid stenosis. Eur J Clin Invest. 1999;29:478-483.
67. Margaglione M, Celentano E, Grandone E, et al. Deletion polymorphism in the angiotensin-converting enzyme gene in patients with a history of ischemic stroke. Arterioscler Thromb Vasc Biol. 1996;16:304-309.
68. Markus HS, Barley J, Lunt R, et al. Angiotensin-converting enzyme gene deletion polymorphism: a new risk factor for lacunar stroke but not carotid atheroma. Stroke. 1995;26:1329-1333.
69. Peterlin B, Petrovic D, Zorc M, Keber I. Deletion/insertion polymorphism in the angiotension-converting enzyme gene as a risk factor in the Slovenian patients with coronary heart disease. Pflugers Arch. 2000;439(suppl):R40-R41.
70. Pfohl M, Fetter M, Koch M, Barth CM, Rudiger W, Haring HU. Association between angiotensin 1-converting enzyme genotypes, extracranial artery stenosis, and stroke. Atherosclerosis. 1998;140:161-166.
71. Sharma P, Carter ND, Barley J, Brown MM. Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme. J Hum Hypertens. 1994;8:645-648.
72. Ueda S, Weir CJ, Inglis GC, Murray GD, Muir KW, Lees KR. Lack of association between angiotensin converting enzyme gene insertion/deletion polymorphism and stroke. J Hypertens. 1995;13:1597-1601.
73. Zee RY, Ridker PM, Stampfer MJ, Hennekens CH, Lindpaintner K. Prospective evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of stroke. Circulation. 1999;99:340-343.
74. Catto AJ, Kohler HP, Bannan S, Stickland M, Carter A, Grant PJ. Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage. Stroke. 1998;29:813-816.
75. Corral J, Gonzalez-Conejero R, Iniesta JA, Rivera J, Martinez C, Vicente V. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica. 2000;85:293-297.
76. Elbaz A, Poirier O, Canaple S, Chedru F, Cambien F, Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood. 2000;95:586-591.
77. Endler G, Funk M, Haering D, et al. Is the factor XIII 34Val/Leu polymorphism a protective factor tor cerebrovascular disease? Br J Haematol. 2003;120:310-314.
78. Gemmati D, Serino ML, Ongaro A, et al. A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases. Am J Hematol. 2001;67:183-188.
79. Reiner AP, Frank MB, Schwartz SM, et al. Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women. Br J Haematol. 2002;116:376-382.
80. Basun H, Corder EH, Guo Z, et al. Apolipoprotein E polymorphism and stroke in a population sample aged 75 years or more. Stroke. 1996;27:1310-1315.
81. Catto AJ, McCormack LJ, Mansfield MW, et al. Apolipoprotein E polymorphism in cerebrovascular disease. Acta Neurol Scand. 2000;101:399-404.
82. Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J. Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease: a case-control study. Stroke. 1993;24:661-664.
83. Frikke-Schmidt R, Nordestgaard BG, Thudium D, Moes Gronholdt ML, Tybjaerg-Hansen A. APOE genotype predicts AD and other dementia but not ischemic cerebrovascular disease. Neurology. 2001;56:194-200.
84. Hachinski V, Graffagnino C, Beaudry M, et al. Lipids and stroke: a paradox resolved. Arch Neurol. 1996;53:303-308.
85. Kessler C, Spitzer C, Stauske D, et al. The apolipoprotein E and β-fibrinogen G/A-455 gene polymorphisms are associated with ischemic stroke involving large-vessel disease. Arterioscler Thromb Vasc Biol. 1997;17:2880-2884.
86. MacLeod MJ, De Lange RP, Breen G, Meiklejohn D, Lemmon H, Clair DS. Lack of association between apolipoprotein E genotype and ischaemic stroke in a Scottish population. Eur J Clin Invest. 2001;31:570-573.
87. Margaglione M, Seripa D, Gravina C, et al. Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian Case-Control Study. Stroke. 1998;29:399-403.
88. Carlsson LE, Greinacher A, Spitzer C, Walther R, Kessler C. Polymorphisms of the human platelet antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GPIIb/Illa), von Willebrand factor (GPIb/IX), and collagen (GPIa/Ila) are not correlated with an increased risk for stroke. Stroke. 1997;28:1392-1395.
89. Carter AM, Catto AJ, Bamford JM, Grant PJ. Association of the platelet glycoprotein lib HPA-3 polymorphism with survival after acute ischemic stroke. Stroke. 1999;30:2606-2611.
90. Kekomaki S, Hamalainen L, Kauppinen-Makelin R, Palomaki H, Kaste M, Kontula K. Genetic polymorphism of platelet glycoprotein Illa in patients with acute myocardial infarction and acute ischaemic stroke. J Cardiovasc Risk. 1999;6:13-17.
91. Reiner AP, Kumar PN, Schwartz SM, et al. Genetic variants of platelet glycoprotein receptors and risk of stroke in young women. Stroke. 2000;31:1628-1633.
92. Reuner KH, Elgas M, Kaps M, Ruf A, Patscheke H. The human platelet antigen HPA-1a/1b (PI(A1)/PI(A2)) polymorphism and cerebral ischaemia [letter]. Thromb Haemost. 1997;78:964-965.
93. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein Illa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet. 1997;349:385-388.
94. van Goor ML, Gomez Garcia E, Brouwers GJ, Leebeek FW, Koudstaal PJ, Dippel DW. PLA1/A2 polymorphism of the platelet glycoprotein receptor Ilb/Illa in young patients with cryptogenic TIA or ischemic stroke. Thromb Res. 2002;108:63-65.
95. Wagner KR, Giles WH, Johnson CJ, et al. Platelet glycoprotein receptor Illa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study. Stroke. 1998;29:581-585.
96. Elbaz A, Poirier O, Moulin T, et al. Association between the Glu298Asp polymorphism in the endothelial constitutive nitric oxide synthase gene and brain infarction. Stroke. 2000;31:1634-1639.
97. MacLeod MJ, Dahiyat MT, Cumming A, Meiklejohn D, Shaw D, St Clair D. No association between Glu/Asp polymorphism of NOS3gene and ischemic stroke. Neurology. 1999;53:418-420.
98. Markus HS, Ruigrok Y, Ali N, Powell JF. Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma. Stroke. 1998;29:1908-1911.
99. Endler G, Lalouschek W, Exner M, Mitterbauer G, Haring D, Mannhalter C. The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls. Br J Haematol. 2000;110:469-471.
100. Hindorff LA, Schwartz SM, Siscovick DS, Psaty BM, Longstreth WT Jr, Reiner AP. The association of PAI-1 promoter 4G/5G insertion/deletion polymorphism with myocardial infarction and stroke in young women. J Cardiovasc Risk. 2002;9:131-137.
101. Roest M, van der Schouw YT, Banga JD, et al. Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mor-tality in older women. Circulation. 2000;101:67-70.
102. Baker RI, Eikelboom J, Lofthouse E, et al. Platelet glycoprotein lbα Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood. 2001;98:36-40.
103. A and GP Ib variable number tandem repeat polymorphisms and markers of platelet activation in acute stroke. Arterioscler Thromb Vasc Biol. 1998;18:1124-1131.
104. Gonzalez-Conejero R, Lozano ML, Rivera J, et al. Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease. Blood. 1998;92:2771-2776.
105. Corral J, Gonzalez-Conejero R, Lozano ML, Rivera J, Vicente V. Genetic polymorphisms of factor VII are not associated with arterial thrombosis. Blood Coagul Fibrinolysis. 1998;9:267-272.
106. Heywood DM, Carter AM, Catto AJ, Bamford JM, Grant PJ. Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality. Stroke. 1997;28:816-821.
107. Corral J, Lozano ML, Gonzalez-Conejero R, et al. A common polymorphism flanking the ATG initiator codon of GPIbα does not affect expression and is not a major risk factor for arterial thrombosis. Thromb Haemost. 2000;83:23-28.
108. Frank MB, Reiner AP, Schwarte SM, et al. The Kozak sequence polymorphism of platelet glycoprotein lbα and risk of nonfatal myocardial infarction and non-fatal stroke in young women. Blood. 2001;97:875-879.
109. Huang P, Kostulas K, Huang WX, Crisby M, Kostulas V, Hillert J. Lipoprotein lipase gene polymorphisms in ischaemic stroke and carotid stenosis. Eur J Clin Invest. 1997;27:740-742.
110. Myllykangas L, Polvikoski T, Sulkava R, et al. Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study. Ann Med. 2001;33:486-492.
111. Wittrup HH, Nordestgaard BG, Sillesen H, Schnohr P, Tybjaerg-Hansen A. A common mutation in lipoprotein lipase confers a 2-fold increase in risk of ischemic cerebrovascular disease in women but not in men. Circulation. 2000;101:2393-2397.
112. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325:1202-1206.
113. Keavney B, McKenzie C, Parish S, et al; International Studies of Infarct Survival (ISIS) Collaborators. Large-scale test of hypothesised associations between the angiotensin-convertlng-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. Lancet. 2000;355:434-442.
114. Keavney B, Parish S, Palmer A, et al. Large-scale evidence that the cardiotoxicity of smoking is not significantly modified by the apolipoprotein E ε2/ε3/ε4 genotype. Lancet. 2003;361:396-398.
115. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64-67.
116. Dahlback B. New molecular insights into the genetics of thrombophilia: resistance to activated protein C caused by Arg506 to Gln mutation in factor V as a pathogenic risk factor for venous thrombosis. Thromb Haemost. 1995;74:139-148.
117. Franco RF, Trip MD, ten Cate H, et al. the 20210 G→A mutation in the 3′-untranslated region of the prothrombin gene and the risk for arterial thrombotic disease. Br J Haematol. 1999;104:50-54.
118. Cattaneo M, Chantarangkul V, Taioli E, Santos JH, Tagliabue L. The G20210A mutation of the prothrombin gene in patients with previous first episodes of deep-vein thrombosis: prevalence and association with factor V G1691 A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels. Thromb Res. 1999;93:1-8.
119. Tiret L, Rigat B, Visvikis S, et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin 1-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992;51:197-205.
120. Sharma P, Carter ND, Barley J, Lunt R, Seymour CA, Brown MM. Polymorphisms in the gene encoding angiotensin 1-converting enzyme and relationship to its post-translational product in cerebral infarction. J Hum Hypertens. 1994;8:633-634.
121. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol. 2000;20:484-492.
122. Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev. 2000;52:11-34.
123. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111-113.
124. Klerk M, Verhoef P, Clarke R, et al; MTHFR Studies Collaboration Group. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002;288:2023-2031.
125. Lellouche F, Dorval I, Dewilde J, Van Walleghem E. Presence of G1691A mutation on the gene of factor V in arterial thrombosis [letter] [in French]. Presse Med. 1995;24:869.
126. Moliaka IuK, Petruk SV, Kir'ianov SA, et al. Association analysis of polymorphism in angiotensin-converting enzyme gene in ischemic stroke [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98:35-37.
127. Pongracz E, Tordai A, Csornai M, Nagy Z. Genetics of blood coagulation in young stroke patients [in Hungarian]. Ideggyogy Sz. 2002;55:111-117.
128. Pongracz E, Tordai A, Csornai M, Nagy Z. Investigation of insertion/deletion polymorphism of the ACE gene in stroke patients [in Hungarian]. Ideggyogy Sz. 2002;55:157-163.
129. Pongracz E, Tordai A, Csornai M, Nagy Z. Platelet glycoprotein llb/llla (LeuPro 33) polymorphism in stroke patients [in Hungarian]. Orv Hetil. 2001;142:781-785.
130. Yang Q, Khoury MJ, Botto L, et al. Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes. Am J Hum Genet. 2003;72:636-649.
131. Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet. 2003;361:865-872.