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Multilocus analysis of the association of polymorphic variants of inflammation genes with ischemic stroke in Russians

  • Genomics. Transcriptomics
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Abstract

Carriage frequencies of alleles and genotypes of polymorphic loci of inflammation genes (49A>G CTLA4, 41G>A and 87C>T PDE4D, −590C>T IL4, −308A>G TNF, 252G>A LTA, 874A>T IFNG, −509С>Т, 869T>C and 915G>C TGFB1) were determined in a sample of 200 patients diagnosed with ischemic stroke and in the control group similar in gender and age (146 individuals), all ethnic Russians. The positive association of the allele PDE4D*87C (р = 0.028) and genotype TGFB1*−509Т/Т (р = 0.02) carriage with ischemic stroke was shown. The association of the disease with the carriage of the allele PDE4D*41А (р = 0.009) in individuals under the age of 60 and with carriage of the allele IFNG*874Т (р = 0.02) in individuals older than 60 was observed among the subgroups of patients stratified by age when they suffered the stroke compared to a control group of the same age. In subgroups stratified by gender, carriage of the genotype TGFB1*915G/G (р = 0.0015) was identified as a risk factor in male patients, while no significant differences between female patients and healthy women were observed. Multilocus analysis was undertaken to search for the association of several combinations of studied gene variants with ischemic stroke. The polymorphic locus–174G>C of the IL6 gene, for which an association with the disease was previously demonstrated, was also included in this analysis. The disease-predisposing biallelic combinations include the IL6*−174G, PDE4D*87C, TGFB1*−509Т and TGFB1*915G alleles. In the subgroups stratified by gender, the allelic combinations mainly include the similar risk alleles as in the total group, while between the subgroups stratified by age (patients who suffered the first stroke at the age of 18 and no older than 60 years and older than 60 years), greater differences were observed. However, a new risk allele, LTA*252G, was identified in combination with PDE4D*41А in women. These findings demonstrate the important role of inflammation in ischemic stroke. The identified single and combined markers may be used further to determine an individual risk for ischemic stroke.

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Abbreviations

CI:

confidence interval

IS:

ischemic stroke

OR:

odds ratio

RFLP:

restriction fragment length polymorphism

PCR:

polymerase chain reaction

PCR-SSP:

sequence specific primer-polymerase chain reaction

CTLA4:

cytotoxic T-lymphocyte-associated protein 4

GWAS:

Genome-Wide Association Studies

LTA:

lymphotoxin-alpha

PDE4D:

phosphodiesterase 4D

rs:

reference sequence

TGFB1:

transforming growth factor beta 1

TNF:

tumor necrosis factor

LD:

linkage disequilibrium

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Authors and Affiliations

  1. Russian Cardiology Scientific and Production Center, Moscow, 121552, Russia

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

  2. Pirogov Russian National Research Medical University, Moscow, 117997, Russia

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

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Original Russian Text © B.V. Titov, N.A. Matveeva, M.Yu. Martynov, O.O. Favorova, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 4, pp. 674–684.

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Titov, B.V., Matveeva, N.A., Martynov, M.Y. et al. Multilocus analysis of the association of polymorphic variants of inflammation genes with ischemic stroke in Russians. Mol Biol 50, 596–605 (2016). https://doi.org/10.1134/S0026893316040142

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  • DOI: https://doi.org/10.1134/S0026893316040142

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