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Ischemic stroke as a complex polygenic disease

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Abstract

Cerebrovascular accidents (strokes) are a challenge to modern health care throughout the world because they contribute greatly to morbidity, disability, and mortality rates. Ischemic stroke constitutes the majority of cases of cerebrovascular accidents. It is a complex multifactorial polygenic disease, i.e., it develops under the influence of conventional risk factors and the genetic component. The latter is formed by the joint contribution of many independent or interacting polymorphic genes. Current studies of the genetic susceptibility to ischemic stroke use two approaches based on the analysis of the association between polymorphic sites of the genome and the disease, including the candidate-gene approach and genome-wide association studies, followed by a meta-analysis of the results. This review considers the published data on genetic susceptibility to ischemic stroke, which may be a starting point for the investigation of molecular mechanisms that determine the pathophysiology of ischemic stroke. Although some progress has been made in this field, the problem of identifying genetic risk factors that could be used as markers for predicting individual susceptibility to ischemic stroke is still far from a complete solution. The main obstacle to this is the low replication of the results. It can be overcome by investigating ethnically uniform populations and clinically distinct IS forms.

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Abbreviations

BP:

blood pressure

AH:

arterial hypertension

CI:

confidence interval

CNV:

copy number variation

CVA:

cardiovascular accident

CVD:

cardiovascular disease

DM:

diabetes mellitus

GWAS:

genome-wide association study

HDL:

high-density lipoprotein

IS:

ischemic stroke

LDL:

low-density lipoprotein

SHRSP:

spontaneously hypertensive stroke-prone rats

SHRSR:

spontaneously hypertensive stroke-resistant rats

SNP:

single nucleotide polymorphism, Th2, type 2 T helper cells

QTL:

quantitative trait locus

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Authors and Affiliations

  1. N.I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, 117997, Russia

    B. V. Titov, N. A. Matveeva, M. Yu. Martynov & O. O. Favorova

  2. Russian Cardiology Research and Production Complex, Ministry of Health of the Russian Federation, Moscow, 121552, Russia

    B. V. Titov, N. A. Matveeva & O. O. Favorova

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  1. B. V. Titov
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  2. N. A. Matveeva
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  3. M. Yu. Martynov
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  4. O. O. Favorova
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Original Russian Text © B.V. Titov, N.A. Matveeva, M.Yu. Martynov, O.O. Favorova, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 2, pp. 224–248.

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Titov, B.V., Matveeva, N.A., Martynov, M.Y. et al. Ischemic stroke as a complex polygenic disease. Mol Biol 49, 195–216 (2015). https://doi.org/10.1134/S0026893315020120

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