The aim of this study was to evaluate the prevalence of factor V Leiden (FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations, and angiotensin-converting enzyme (ACE) I/D polymorphism in ischemic stroke (IS) patients. A total of 162 Turkish IS patients were included and analyzed according to stroke subtype by the TOAST classification. Their genotype data were compared with those of the control group, representing the healthy population, using the χ2 test. The frequency of FVL heterozygocity was 12.3% in this series—higher than that in the normal population (9.8%; statistically insignificant, P = .478). The frequency of the ACE D/D genotype in all stroke patients and those with stroke of undetermined etiology was higher than that in our population (52.5% and 59.2%, respectively, vs 39.3%; statistically significant, P = .034, P = .020). Our results may suggest that ACE D/D genotype is a risk factor for IS, particularly in those with stroke of undetermined etiology in the Turkish population.
Tournier-Laserve E.New players in the genetic of stroke. N Eng J Med. 2002;347:1711-1712.
2.
Gao X., Yang H., ZhiPing T.Association studies of genetic polymorphism, environmental factors and their interaction in ischemic stroke. Neurosci Lett. 2006;398:172-177.
3.
Bezemer ID, Rosendaal FRPredictive genetic variants for venous thrombosis: what’s new ? Semin Hematol. 2007;44:85-92.
4.
Dahlbäck B., Carlsson M., Svensson PJFamilial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci. 1993;90:1004-1008.
5.
Atac B., Yakupoglu U., Ozbek N., Ozdemir FN, Bilgin N.Role of genetic mutations in vascular access thrombosis among hemodialysis patients waiting for renal transplantation. Transplant Proc . 2002;34:2030-2032.
6.
Slowik A., Dziedzic T., Pera J., Wloch D., Kopec G., Szczudlik A.ACE genotype, risk and causal relationship to stroke: implications for treatment . Curr Treat Options Cardiovasc Med. 2007;9:198-204.
7.
Carluccio M. , Soccio M., de Caterina R.Aspects of gene polymorphism in cardiovascular disease: the renin-angiotensin system. Eur J Clin Invest. 2001;31:476-488.
8.
Adams HP, Bendixen BH, Keppelle J., et al. Classification of ischemic stroke: definition for use in a multicenter clinical trial. Stroke. 1993;24:35-41.
9.
Miller SA, Dykes DD, Polesky HSA simple salting out procedure for extracting DNA from human nucleated cells . Nucleic Acids Res. 1988;16:1215.
10.
De Stefano V., Zappacosta B., Persichilli S., et al. Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease. Br J Haematol. 1999 ;106:564-568.
11.
Akar N., Akar E., Akçay R., Avcu F., Yalççn A., Cin S.Effect of methylenetetrahydrofolate reductase 677 C-T, 1298 A-C, and 1317 T-C on factor V 1691 mutation in Turkish deep vein thrombosis patients . Thromb Res. 2000;97:163-167.
12.
Lovati E., Richard A., Frey BM, Frey FJ, Ferrari P.Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int. 2001 ;60:46-54.
13.
Akar N., Akar E., Dalg1n G., Sözüöz A., Ömürlü K., Cin S.Frequency of Factor V (1691 G>A) mutation in Turkish population . Thromb Haemost. 1997;78:1527-1529.
14.
Akar N., M1s1rl1oglu M., Akar E.Prothrombin gene 20210 G-A mutation in the Turkish population. Am J Haematol. 1998;58:249.
15.
Akar N., Akar E., Deda G., Sipahi T., Orsal A.Factor V1691 G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct. J Child Neurol. 1999;14: 749-1751.
16.
Akar N., Aras Ö., Ömürlü K., Cin S.Deletion polymorphism at the angiotensin-converting enzyme gene in Turkish patients with coronary artery disease. Scand J Clin Lab Invest . 1998;58:491-496.
17.
Lovett JK, Coull AJ, Rothwell PMEarly risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology. 2004:62;569-573.
18.
Sharma P.Meta-analysis of the ACE gene ischaemic stroke. J Neurol Neurosurg Psychiatry. 1998;64:227-230.
19.
Markus HS, Barley J., Lunt R., et al. Angiotensin converting enzyme gene deletion polymorphism: a new risk factor for lacuner stroke but no carotid atheroma. Stroke. 1995;26:1329-1333.
20.
Nakata Y., Katsuya T., Rakugi H., et al. Polymorphism of angiotensin-converting enzyme, angiotensinogen, and Apolipoprotein E genes in a Japanese population with cerebrovascular disease . Am J Hypertens. 1997;12:1391-1395.
21.
Doi Y., Yoshinari M., Yoshizumi H., Ibayashi S., Wakisaka M., Fujishima M.Polymorphism in the angiotensin- converting enzyme (ACE) gene in patients with thrombotic brain infarction. Atherosclerosis. 1997;132:145-150.
22.
Kario K., Kanai N., Saito K., Nago N., Takefumi M., Shimada K.Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives. Circulation. 1996;93:1630-1633.
23.
Watanabe Y. , Ishigami T., Kawano Y., et al. Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese. Hypertension . 1997;30:569-573.
24.
Castellano M., Muiesan ML, Rizzoni D., et al. Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population . Circulation. 1995;91: 2721-2724.
25.
Reed DC, Cox M., Clegg JBWorld distribution of factor V Leiden. Lancet. 1995;346:1133-1134.
26.
Rosendaal FR , Koster T., Vandenbroucke JP, Reistma PHHigh risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood . 1995;85:1504-1508.
27.
Alboucher JF , Guirand-Chaumeil B., Chollet F., Cadroy Y., Sie P.Frequency of resistance to activated protein C due to factor V mutation in young patients with ischaemic stroke (letter). Stroke. 1996;27:766-767.
28.
Chimowitz M. , Mansbach H., Schmaier A.Factor V mutation and cryptogenic stroke in the young [abstract]. Stroke. 1996;27:188.
29.
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.
30.
Ridker PM, Hennekens CH, Lidpaintner K., Stampfer MJ, E1senberg PR, Miletich JPMutation 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.
31.
Fisher M., Fernandez JA, Ameriso SF, et al. Activated protein C resistance in ischemic stroke not due to factor V arginine506→glutamine mutation. Stroke. 1996;27: 1163-1166.
32.
Press RD, Liu XY, Beamer N., Coull BMIschemic stroke in the elderly: role of the common factor V mutation causing resistance to activated protein C. Stroke. 1996;27:44-48.
33.
Sánchez J., Román J., de la Torre M., Velasco F., Torres A.Low prevalance of the factor V Leiden among patients with ischemic stroke. Haemostasis. 1997;27:9-15.
34.
Longstreth WT, Rosendaal FR, Siscovick DS, et al. Risk of stroke in young women and two prothrombotic mutation: factor V Leiden and prothrombin gene variant (G20210A) . Stroke. 1998;29:577-580.
35.
Markus HS, Zhang Y., Jeffery S.Screening for the factor V Arg506 Gln mutation in patients with TIA and stroke . Cerebrovasc Dis. 1996;6:360-362.
36.
Rosendaal FR , Doggen CJ, Zivelin A., et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost. 1998;79:706-708.
37.
Cumming AM, Keeney S., Salden A., Bhavnani M., Shwe K., Hay CRM.The prothrombin gene G20210A variant: prevalance in a U.K. anticoagulant clinic population. Br J Haemotol. 1997;98:353-355.
38.
De Stefano V., Chiusulo P., Paciaroni K., et al. Prothrombin G20210A mutation genotype is a risk factor for cerebrovascular ischemic disease in young patients. Blood. 1998;91:3562-3565.
39.
Martinelli I., Franchi F., Akwan S., Bettini P., Merati G., Mannucci PMThe transition G to A at position 20210 in the 3’ untranslated region of the prothrombin gene is not associated with cerebral ischaemia. Blood. 1997; 29:3806.
40.
Perry IJ, Refsum H., Morris RW, Ebrahim SB, Ueland PM, Shaper AGProspective study of serum total homocysteine concentration and risk of stroke in middle-agedBritish men. Lancet. 1995;346:395-398.
41.
Markus HS, Ali N., Swaminathan R., Sankaralingam A., Molloy J., Powell J.A common polymorphism in the methylentetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke . 1997;28: 1739-1743.
42.
Nakata Y., Katsuya T., Takami S., et al. Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease. Am J Hypertens . 1998;11:1019-1023.
