Study of associations of polymorphic variants of lipid metabolism genes and angiogenesis with first ischemic stroke

Cover Page

Cite item

Full Text

Abstract

Introduction. Ischemic stroke (IS) is a complex multifactorial disorder with heterogeneous congenital component. Polymorphic variants of genes of apolipoprotein В (APOB), apolipoprotein А-V (APOА-V), apolipoprotein С-IV (APOC-IV), apolipoprotein H (APOH), apolipoprotein D (APOD), angiopoietin-related protein 4 (ANGPT4) that regulate lipid metabolism and vascular regeneration, may be regarded as perspective ones. Although until recently they were not studied in complex, in a homogenous group from the perspective of possible association with first IS development. Aim. To study association between polymorphic variants of the following genes: АРОH, APOD, APOE, APOA5, APOC4, ANGPT4 and first IS development. Materials and methods. Frequencies of alleles and genotypes of single nucleotide polymorphic gene variants in 200 patients after first IS and in 115 people without stroke matched by sex, age and place of residence were studied. Blood was taken from all study participants in order to perform genotyping assay using protocol by J.Hixson and D.Vernier. Genomic deoxyribonucleic acid extraction from blood was performed using magnetic beads technology on an automated system for nucleic acid extraction Chemagen Prepito (ABBIS, Germany). For single nucleotide polymorphisms typing alleles identification analysis was performed using polymerase chain reaction with prepared TaqMan probes with Assey ID identification number (Applied Biosystems, USA). Amplification of polymorphic regions of the genes was performed with the use of 7500 Real-Time PCR System (Applied Biosystems, USA). Standard amplification conditions were used that were compatible with those defined by chemical agents supplier for each Assey ID. Genotypes nomenclature is given in accordance with international database db SNP (https://www.ncbi.nlm.nih.gov/SNP/). Results. Significant differences between groups in distribution of minor alleles and genotypes were acquired for АРОD (rs7659) and APOA5 (rs619054) polymorphisms. Conclusion. Significant association of single nucleotide АРОD (rs7659) and APOA-V (rs619054) genes polymorphisms with first IS development was found in study groups.

About the authors

Veronika N. Shishkova

Center for Speech Pathology and Neurorehabilitation; A.I.Yevdokimov Moscow State University of Medicine and Dentistry

Email: veronika-1306@mail.ru
Cand. Sci. (Med.), Senior Res. Officer

Alla Yu. Remennik

Center for Speech Pathology and Neurorehabilitation

Cand. Sci. (Med.)

Vera V. Valyaeva

Center for Speech Pathology and Neurorehabilitation

doctor-laboratory assistant

Tatiana V. Adasheva

A.I.Yevdokimov Moscow State University of Medicine and Dentistry

D. Sci. (Med.), Prof.

Ludmila V. Stakhovskaya

Pirogov Russian National Research Medical University

D. Sci. (Med.), Prof.

Ludmila A. Skipetrova

Center for Speech Pathology and Neurorehabilitation

Deputy Chief doctor

Roman A. Cheremin

Center for Speech Pathology and Neurorehabilitation

Cand. Sci. (Med.)

Viktor M. Shklovskii

Center for Speech Pathology and Neurorehabilitation

Full Prof.

References

  1. Гусев Е.И., Скворцова В.И., Стаховская Л.В. Проблема инсульта в Российской Федерации: время активных совместных действий. Журн. неврологии и психиатрии. 2007; 8: 4-10.
  2. Стаховская Л.В, Котов С.В., Исакова Е.В. Инсульт: руководство для врачей. Под общ. ред. Л.В.Стаховской. М.: Мед. информ. агентство, 2013.
  3. Скворцова В.И., Шетова И.М., Шамалов Н.А. и др. Анализ ассоциации ДНК-маркеров с риском развития церебрального инсульта у лиц из славянской популяции. Вестн. Российского государственного медицинского университета. 2011; 6: 62-6.
  4. Торшин И.Ю., Громова О.А., Никонов А.А. Гены и цереброваскулярная патология, гены и нуклеотидные полиморфизмы при отдельных видах физиологических сдвигов и патологических процессов. Журн. неврологии и психиатрии (Прил. «Инсульт»). 2009; 5: 77-83. [
  5. Limborska S, Khrunin A, Verbenko D. Minisatellite DNA Markers in Population Studies. In: Population genetics. Ed. M.Carmen Fust. Intech, Rijeka, 2012; p. 55-86.
  6. Боринская С.А., Кальина Н.Р., Санина Е.Д. Полиморфизм гена аполипопротеина Е в популяциях России и сопредельных стран. Генетика. 2007; 43 (10): 1434-9.
  7. Заседателев А.С., Скворцова В.И. Анализ ассоциации полиморфных маркеров генов ренин-ангиотензиновой системы и системы гемостаза с ишемическим инсультом среди русских Центральной России. Молекулярная биология. 2012; 46 (2): 214-23.
  8. Шишкова В.Н., Адашева Т.В., Ременник А.Ю. и др. Изучение ассоциаций полиморфных вариантов генов липидного и углеводного обменов, сосудистого воспаления и нейротрансмиттерных систем с развитием первого ишемического инсульта. Кардиоваскулярная терапия и профилактика. 2017; 16 (5): 27-31.
  9. Авдонина М.А., Наседкина Т.В., Иконникова А.Ю. и др. Исследование ассоциации полиморфных маркеров генов F12, PON1, PON2, NOS2, PDE4D, HIFla, GPIba, CYP11B2 с ишемическим инсультом среди русского населения Центральной России. Журн. неврологии и психиатрии им. С.С.Корсакова. 2012; 112 (2): 51-4.
  10. Fornage M. Genetics of stroke. Curr Atheroscler Rep 2009; 11: 167-74.
  11. Matarin M, Brown W.M, Dena H et al. Candidate gene polymorphisms for ischemic stroke. Stroke 2009; 40: 3436-42.
  12. Dichgans M, Hegele R.A. Update on the genetics of stroke and cerebrovascular disease 2008. Stroke 2009; 40: 289-91.
  13. Парфенов М.Г., Титов Б.В., Судомоина М.А. и др. Комплексный анализ генетической предрасположенности к ишемическому инсульту у русских. Молекулярная биология. 2009; 43: 937-45.
  14. Hixson J.E, Vernier D.T. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990; 31 (3): 545-8.
  15. Lövkvist H, Jönsson A.C, Luthman H et al. Variations in apoapolipoprotein D and sigma non-opioid intracellular receptor 1 genes with relation to risk, severity and outcome of ischemic stroke. BMC Neurology 2014; 14: 191-200.
  16. Camato R, Marcel Y.L, Milne R.W et al. Protein polymorphism of human plasma apolipoprotein D antigenic epitope. J Lipid Res 1989; 30 (6): 865-75.
  17. Waldner A, Dassati S, Redl B et al. Apolipoprotein D concentration in human plasma during adding and in Parkinson’s disease: a cross-sectional study. Perkinsons Dis 2018; article ID 3751516.
  18. Pedro-Botet J, Senti M, Nogues X et al. Lipoprotein and apolipoprotein profile in men with ischemic stroke. Stroke 1992; 23 (11): 1556-62.
  19. Сизов А.В., Гавабри К.Г., Ковалев Ю.Р. и др. Гиперлипидемия V типа. Медицина: теория и практика. 2017; 2 (2): 9-13.
  20. Wang Y, Liu F, Li L et al. The association between apolipoprotein A1-C3-A5 gene cluster promoter polymorphisms and risk of ischemic stroke in the northern Chinese Han population. J Int Med Res 2017; 45 (6): 2042-52.
  21. Pi Y, Zhang L, Yang Q et al. Apolipoprotein A5 gene promoter region-1131T/C polymorphism is associated with risk of ischemic stroke and elevated triglyceride levels: a meta-analysis. Cerebrovasc Dis 2012; 33 (6): 558-65.
  22. Járomi L, Csöngei V, Polgár N et al. Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke. J Mol Neurosci 2010; 41 (1): 121-8.
  23. Diakite B, Hamzi K, Hmimech W et al. Genetic polymorphisms of T-1131C ApoA5 and ALOX5AP SG13S114 with the susceptibility of ischemic stroke in Morocco. J Genet 2016; 95 (2): 303-9.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2019 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).