Genetic variants in HSP70-family and BAG co-chaperone genes, particularly BAG1 rs706121, BAG3 rs196329, and HSPA6 rs753856, were associated with coronary artery disease risk in a Russian cohort, with associations modified by sex and lifestyle factors.
The C allele of BAG1 rs706121 was associated with increased CAD risk in the overall study population.
The C allele of BAG1 rs706121 was associated with increased CAD risk specifically in males.
The C allele of BAG1 rs706121 was associated with increased CAD risk in smokers.
The A allele of BAG3 rs196329 was associated with lower CAD risk in males.
The G allele of HSPA6 rs753856 was associated with reduced CAD risk in physically active individuals.
Additional associations between the studied SNPs and clinical or biochemical traits related to CAD were identified.
Functional annotation of the identified loci revealed potential regulatory effects including eQTL associations, overlap with histone marks, and allele-dependent changes in transcription factor binding.
HSP70 family proteins and BAG co-chaperones regulate biological processes central to CAD pathogenesis including oxidative stress, inflammation, apoptosis, and ischemia responses.
This research suggests that certain genetic variants in genes encoding heat shock proteins (HSP70 family) and their helper proteins (BAG co-chaperones) are linked to the risk of developing coronary artery disease (CAD), which is a leading cause of heart attacks. The study examined 13 genetic variants in 834 CAD patients and 1328 healthy controls from Russia. Three variants stood out: a variant in the BAG1 gene increased CAD risk overall and was particularly relevant in men and smokers; a variant in the BAG3 gene appeared to lower risk in men; and a variant in the HSPA6 gene was associated with substantially lower risk (about 39% lower odds) in physically active people. An important feature of the findings is that the genetic associations were not uniform across all people — they differed depending on sex and lifestyle factors like smoking and physical activity. This suggests that the impact of these genetic variants on heart disease risk may depend on a person's broader context. The researchers also used computational tools to explore how these genetic variants might work biologically, finding that they could influence gene activity by affecting how genes are regulated, including changes in which proteins bind to DNA and how DNA is packaged in cells. This research suggests that variants in stress-response genes like HSP70 and BAG family members may play a role in heart disease susceptibility and could potentially contribute to more personalized approaches to understanding CAD risk that take into account both genetics and lifestyle. However, as this is a single-population case-control study, replication in other populations would be needed to confirm and generalize these findings.
Polshvedkina O, Kobzeva K, Orlov Y, Bushueva O. (2026). Genetic Variants in HSP70 Family and BAG Co-Chaperone Genes: Associations with Coronary Artery Disease Risk and Potential Regulatory Effects.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167299