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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Genetic Variants in HSP70 Family Genes and Their Co-Chaperones Are Associated with Ischemic Stroke Susceptibility and Gene Expression During Acute and Early Recovery Phases

  • Maxim Ivenkov1,2
  • Anastasiya Snezhkina3
  • Irina Shilenok1
  • Nataliya Medvedenko1,2
  • Aleksei Zarubin4
  • Egor Bushuev1,5
  • Ulyana Dubinina1,5
  • Ksenia Kobzeva1
  • Anna Kudryavtseva3
  • Yury Nechipurenko3,6
  • Olga Bushueva1,5
6 affiliations
  1. 1Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia
  2. 2Department of Neurology and Neurosurgery, Kursk State Medical University, 305041 Kursk, Russia
  3. 3Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
  4. 4Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia
  5. 5Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 305041 Kursk, Russia
  6. 6Research Institute for Brain Development and Peak Performance, Peoples’ Friendship University of Russia, 117198 Moscow, Russia
Open at sourceDOICite

Abstract

Heat shock protein 70 (HSP70) family members and co-chaperones participate in cellular stress responses, proteostasis, apoptosis, inflammation, and mitochondrial function implicated in ischemic stroke (IS). We investigated associations between genetic variants in HSP70 family genes and BAG co-chaperones and IS susceptibility, clinical characteristics, and gene expression. Twenty-three single-nucleotide polymorphisms were analyzed in 768 patients with IS and 794 controls. Functional annotation included eQTL resources, protein–protein interaction analyses, and targeted genotype–expression analysis of paired peripheral-blood transcriptomes from 19 patients during acute IS and on day 7. In the overall cohort, the variants rs2227956 in HSPA1L and rs7749960 variant in the BAG2 gene were associated with reduced IS risk. The variants rs2227956 and rs2075799 in HSPA1L, rs753856 in HSPA6, rs706121 in BAG1, rs7749960 in BAG2, and rs196329 in BAG3 were linked to IS risk, associations specific to certain subgroups. Additional variants were associated with age at IS onset, lipid levels, coagulation parameters, body mass index, and number of IS episodes. Functional analyses linked associated loci to pathways relevant to atherosclerosis, inflammation, apoptosis, oxidative stress, autophagy, mitochondrial dysfunction, and angiogenesis. Transcriptomic analysis identified associations of rs1043618 HSPA1A with C4B expression during acute IS and DDR1 expression on day 7, while rs1042665 HSPA9 was associated with genotype-dependent changes in HSPA9 expression. These findings support a role for HSP70-related genetic variation in IS susceptibility, clinical heterogeneity, and phase-specific gene-expression differences.

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Cite

BibTeXRIS
BibTeX
@article{ivenkov2026genetic,
  title = {{Genetic Variants in HSP70 Family Genes and Their Co-Chaperones Are Associated with Ischemic Stroke Susceptibility and Gene Expression During Acute and Early Recovery Phases}},
  author = {Maxim Ivenkov and Anastasiya Snezhkina and Irina Shilenok and Nataliya Medvedenko and Aleksei Zarubin and Egor Bushuev and Ulyana Dubinina and Ksenia Kobzeva and Anna Kudryavtseva and Yury Nechipurenko and Olga Bushueva},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219560},
  url = {https://www.mdpi.com/1422-0067/27/21/9560},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Genetic Variants in HSP70 Family Genes and Their Co-Chaperones Are Associated with Ischemic Stroke Susceptibility and Gene Expression During Acute and Early Recovery Phases
AU  - Maxim Ivenkov
AU  - Anastasiya Snezhkina
AU  - Irina Shilenok
AU  - Nataliya Medvedenko
AU  - Aleksei Zarubin
AU  - Egor Bushuev
AU  - Ulyana Dubinina
AU  - Ksenia Kobzeva
AU  - Anna Kudryavtseva
AU  - Yury Nechipurenko
AU  - Olga Bushueva
PY  - 2026
DA  - 2026/10/26
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219560
UR  - https://www.mdpi.com/1422-0067/27/21/9560
AB  - Heat shock protein 70 (HSP70) family members and co-chaperones participate in cellular stress responses, proteostasis, apoptosis, inflammation, and mitochondrial function implicated in ischemic stroke (IS). We investigated associations between genetic variants in HSP70 family genes and BAG co-chaperones and IS susceptibility, clinical characteristics, and gene expression. Twenty-three single-nucleotide polymorphisms were analyzed in 768 patients with IS and 794 controls. Functional annotation included eQTL resources, protein–protein interaction analyses, and targeted genotype–expression analysis of paired peripheral-blood transcriptomes from 19 patients during acute IS and on day 7. In the overall cohort, the variants rs2227956 in HSPA1L and rs7749960 variant in the BAG2 gene were associated with reduced IS risk. The variants rs2227956 and rs2075799 in HSPA1L, rs753856 in HSPA6, rs706121 in BAG1, rs7749960 in BAG2, and rs196329 in BAG3 were linked to IS risk, associations specific to certain subgroups. Additional variants were associated with age at IS onset, lipid levels, coagulation parameters, body mass index, and number of IS episodes. Functional analyses linked associated loci to pathways relevant to atherosclerosis, inflammation, apoptosis, oxidative stress, autophagy, mitochondrial dysfunction, and angiogenesis. Transcriptomic analysis identified associations of rs1043618 HSPA1A with C4B expression during acute IS and DDR1 expression on day 7, while rs1042665 HSPA9 was associated with genotype-dependent changes in HSPA9 expression. These findings support a role for HSP70-related genetic variation in IS susceptibility, clinical heterogeneity, and phase-specific gene-expression differences.
SN  - 1422-0067
ER  -