nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2012-419nnp-159Research ArticleArticlesСтатьиAnalysis of the contribution of -5t/c polymorphism in the GP1BA gene to the development of ischemic stroke in young patientsАнализ вклада -5Т/С-полиморфизма гена GP1BA в развитие ишемического инсульта у пациентов молодого возрастаSkvortsovaV ISkvortsovaV I

Department of Fundamental and Clinical Neurology

Department of Fundamental and Clinical Neurology

-KoltsovaE AKoltsovaE A

Department of Fundamental and Clinical Neurology

Department of Fundamental and Clinical Neurology

-KimelfeldEkaterina IgorevnaKimelfeldEkaterina Igorevna

Department of Fundamental and Clinical Neurology

Department of Fundamental and Clinical Neurology

ekovita@mail.ruLimborskayaS ALimborskayaS A-SlominskyP ASlominskyP A-TupitsynaT VTupitsynaT V-20121512201244NO4 (2012)3944Copyright © Skvortsova V.I., Koltsova E.A., Kimelfeld E.I., Limborskaya S.A., Slominsky P.A., Tupitsyna T.V., 20122012Skvortsova V.I., Koltsova E.A., Kimelfeld E.I., Limborskaya S.A., Slominsky P.A., Tupitsyna T.V.Skvortsova V.I., Koltsova E.A., Kimelfeld E.I., Limborskaya S.A., Slominsky P.A., Tupitsyna T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/159

The impact of -5T/C polymorphism in the GP1BA gene on the risk of ischemic stroke (IS) was studied in patients younger than 50 years of age. Ninety-two patients (73 men and 19 women; mean age 42.6+6.7years) with atherothrombotic, lacunar, and cryptogenic IS were examined on days 1—21 after its development. All the patients underwent brain magnetic resonance imaging or computed tomography, brachiocephalic artery duplex scanning, echocardiography, and laboratory studies (antiphospholipid antibodies, coagulogram and platelet aggregation, homocysteine, clinical and biochemical blood analyses, rheumatic tests, determination of -5T/C polymorphism in the GP1BA gene). An increased risk for IS was found in the young males versus the controls (healthy individuals; p = 0.03; OR 2.7; CI 1.14; 6.47). This association was not found in the women. Analysis of pathogenetic types ascertained that the lacunar IS men with CC and CT genotypes had a higher risk for stroke than the healthy individuals (p = 0.04, OR 3.5, CI 1.1; 10.9). In other subtypes of stroke, there was no association with this polymorphism. A group of patients with IS caused by thrombosis of the great arteries of the brain. In this group, the patients had CC and CT genotypes significantly more frequently than the controls (p = 0.003; OR 6.7; CI 2.0; 21.8), as well as C allele (p = 0.0008; OR 5.1; CI 1.97; 13.3). The -5T/C polymorphism in the GP1BA gene was associated with the development of IS in young males. The -5C allele and -5T/C and -5C/C genotypes are increased risk factors for lacunar and arterial thrombosis-induced IS in men.

Проводилось изучение влияния -5Т/С-полиморфизма гена GP1BA на риск развития ишемического инсульта (ИИ) у больных моложе 50 лет. Обследованы 92 пациента молодого возраста (73 мужчины и 19 женщин, средний возраст — 42,6±6,7года) с атеротромботическим, лакунарным и «криптогенным» ИИ. Обследование проводили на 1-21-й день после развития ИИ. Всем больным выполняли магнитно-резонансную или компьтерную томографию головного мозга, дуплексное сканирование брахиоцефальных артерий, эхокардиографию, а также лабораторные исследования (антитела к фосфолипидам, коагулограмма и агрегация тромбоцитов, гомоцистеин, клинический и биохимический анализ крови, ревматические пробы, определение -5Т/С-полиморфизма гена GP1BA). Выявлено увеличение риска развития ИИ у мужчин молодого возраста с генотипами СС и СТ по сравнению с контролем (здоровые; p=0,03; ОШ 2,7; ДИ 1,14; 6,47). У женщин данной ассоциации не обнаружено. При анализе патогенетических вариантов установлено, что у мужчин с лакунарным ИИ, имеющих генотипы СС и СТ, по сравнению со здоровыми повышен риск развития инсульта (p=0,04, ОШ 3,5, ДИ 1,1; 10,9). При других подтипах инсульта не выявлено ассоциации с данным полиморфизмом. Отдельно проанализирована группа пациентов с ИИ, вызванным тромбозом магистральных артерий головы. В этой группе больных достоверно чаще встречались генотипы СС и СТ по сравнению с контролем (p=0,003; ОШ 6,7 ДИ 2,0; 21,8), а также аллель С (p=0,0008; ОШ 5,1; ДИ 1,97; 13,3). -5Т/С-полиморфизм гена GP1BA ассоциирован с развитием ИИ у мужчин молодого возраста. Аллель -5С и генотипы -5Т/С и -5С/С являются факторами повышенного риска лакунарного подтипа ИИ и ИИ в результате артериального тромбоза у мужчин.

ишемический инсультмолодой возрастполиморфизм гена GP1BAischemic strokeyoung ageGP1BA gene polymorphismReferences<div><p>Donnan G.A., Fisher M., Macleod M. et al. Stroke. Lancet 2008;371(9624):1612-23.</p><p>Верещагин Н.В. Патология вертебробазилярной системы и нарушение мозгового кровообращения. М.: Медицина, 1980;310.</p><p>Asplund K. European White Book on Stroke. Springer, 1998.</p><p>Деев А.С., Захарушкина И.В. Церебральные инсульты в молодом возрасте. Журн неврол и психиатр 2000;1:14-7.</p><p>Putaala J., Metso A.J., Metso T.M. et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke the Helsinki young stroke registry. Stroke 2009;40(4):1195—203.</p><p>Kristensen B., Malm J., Carlberg B. et al. Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in Northern Sweden. Stroke 1997;28(9):1702-9.</p><p>Rasura M., Spalloni A., Ferrari M. et al. A case series of young stroke in Rome. Eur J Neurol 2006;13(2):146—52.</p><p>Kaski S., Kekomaki R., Partanen J. Systemic screening for genetic polymorphism in human platelet glycoprotein Ib-alpha. Immunogenetics 1996;44:170-6.</p><p>Afshar-Kharghan V., Khoshnevis-Asl M., Hopkins P. et al. Polymorphism of the platelet glycoprotein (GP)Ib alpha Kozak sequence determines the surface level of the GPIb- IX-V complex and risk for early myocardial infarction. Blood 1998;92:А2887.</p><p>Afshar-Kharghan V., Li C.Q., Khoshnevis-Asl M. et al. Kozak sequence polymorphism of the glycoprotein (GP) Ibalpha gene is a major determinant of the plasma membrane levels of the platelet GP Ib-IX-V complex. Blood 1999;94(1):186-91.</p><p>Croft S.A., Hampton K.K., Daly M.E. et al. Kozak sequence polymorphism in the platelet GPIbalpha gene is not asso- ciated with risk of myocardial infarction. Blood 2000;95:2183-4.</p><p>Charakida M., Tousoulis D., Stefanadis C. et al. The Role of Platelet Glycoprotein Ib and Iib Polymorphism in Coronary Artery Disease. Hellenic J Cardiol 2003;44:43-8.</p><p>Handa M., Titani K., Holland L.Z. et al. The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. J Biol Chem 1986;261:12579-85.</p><p>Kandzari D.E., Goldschmidt-Clermont P.J. Platelet polymorphisms and ischemic heart disease: moving beyond traditional risk factors. J Am Coll Cardiol 2001;38:1028-32</p><p>Lefkovits J., Plow E.F., Topol E.J. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl Med 1995;332:1553-9.</p><p>Lane D.A., Grant P.J. Role of hemostatic gene polymor phisms in venous and arterial thrombotic disease. Blood 2000;95:1517-32.</p><p>Baker R.I., Eikelboom J., Lofthouse E. et al. Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood 2001;98(1):36—40.</p><p>Frank M.B., Reiner A.P., Schwartz S.M. et al. The Kozak sequence polymorphism of platelet glycoprotein Ibalpha and risk of nonfatal myocardial infarction and nonfatal stroke in young women. Blood 2001;97(4):875—9.</p><p>Esen F.I., Hancer V.C. Glycoprotein Ibalpha Kozak polymorphism in ischemic stroke. Neurol Res 2012;34(1):68—71.</p><p>Adams H.P., Bendixen B.H., Kappelle L.J. et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24(1):35—41.</p></div><br /><div><p>Donnan G.A., Fisher M., Macleod M. et al. Stroke. Lancet 2008;371(9624):1612-23.</p><p>Верещагин Н.В. Патология вертебробазилярной системы и нарушение мозгового кровообращения. М.: Медицина, 1980;310.</p><p>Asplund K. European White Book on Stroke. Springer, 1998.</p><p>Деев А.С., Захарушкина И.В. Церебральные инсульты в молодом возрасте. Журн неврол и психиатр 2000;1:14-7.</p><p>Putaala J., Metso A.J., Metso T.M. et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke the Helsinki young stroke registry. Stroke 2009;40(4):1195—203.</p><p>Kristensen B., Malm J., Carlberg B. et al. Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in Northern Sweden. Stroke 1997;28(9):1702-9.</p><p>Rasura M., Spalloni A., Ferrari M. et al. A case series of young stroke in Rome. Eur J Neurol 2006;13(2):146—52.</p><p>Kaski S., Kekomaki R., Partanen J. Systemic screening for genetic polymorphism in human platelet glycoprotein Ib-alpha. Immunogenetics 1996;44:170-6.</p><p>Afshar-Kharghan V., Khoshnevis-Asl M., Hopkins P. et al. Polymorphism of the platelet glycoprotein (GP)Ib alpha Kozak sequence determines the surface level of the GPIb- IX-V complex and risk for early myocardial infarction. Blood 1998;92:А2887.</p><p>Afshar-Kharghan V., Li C.Q., Khoshnevis-Asl M. et al. Kozak sequence polymorphism of the glycoprotein (GP) Ibalpha gene is a major determinant of the plasma membrane levels of the platelet GP Ib-IX-V complex. Blood 1999;94(1):186-91.</p><p>Croft S.A., Hampton K.K., Daly M.E. et al. Kozak sequence polymorphism in the platelet GPIbalpha gene is not asso- ciated with risk of myocardial infarction. Blood 2000;95:2183-4.</p><p>Charakida M., Tousoulis D., Stefanadis C. et al. The Role of Platelet Glycoprotein Ib and Iib Polymorphism in Coronary Artery Disease. Hellenic J Cardiol 2003;44:43-8.</p><p>Handa M., Titani K., Holland L.Z. et al. The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. J Biol Chem 1986;261:12579-85.</p><p>Kandzari D.E., Goldschmidt-Clermont P.J. Platelet polymorphisms and ischemic heart disease: moving beyond traditional risk factors. J Am Coll Cardiol 2001;38:1028-32</p><p>Lefkovits J., Plow E.F., Topol E.J. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl Med 1995;332:1553-9.</p><p>Lane D.A., Grant P.J. Role of hemostatic gene polymor phisms in venous and arterial thrombotic disease. Blood 2000;95:1517-32.</p><p>Baker R.I., Eikelboom J., Lofthouse E. et al. Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood 2001;98(1):36—40.</p><p>Frank M.B., Reiner A.P., Schwartz S.M. et al. The Kozak sequence polymorphism of platelet glycoprotein Ibalpha and risk of nonfatal myocardial infarction and nonfatal stroke in young women. Blood 2001;97(4):875—9.</p><p>Esen F.I., Hancer V.C. Glycoprotein Ibalpha Kozak polymorphism in ischemic stroke. Neurol Res 2012;34(1):68—71.</p><p>Adams H.P., Bendixen B.H., Kappelle L.J. et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24(1):35—41.</p></div><br />

The authors declare that there are no conflicts of interest present.