Genetic Variants in HSP70 Family and BAG Co-Chaperone Genes: Associations with Coronary Artery Disease Risk and Potential Regulatory Effects

Heat shock proteins of the HSP70 family and their BAG co-chaperones regulate responses to oxidative stress, inflammation, apoptosis, and ischemia, all central to coronary artery disease (CAD) pathogenesis. The contribution of genetic variants within HSP70-family and BAG co-chaperone genes to CAD susceptibility remains unclear. Thus, we sought to evaluate associations of HSP70- and BAG-related SNPs with CAD risk and to characterize their potential regulatory effects using comprehensive bioinformatic analyses. A case–control cohort of 834 CAD patients and 1328 controls of Russian ethnicity was genotyped for 13 SNPs. Associations with CAD susceptibility and traits were tested using log-additive regression with adaptive permutation. Loci underwent functional annotation. The C allele of BAG1 rs706121 was associated with increased CAD risk overall (OR = 1.24, pperm = 0.019), in males (OR = 1.39, pperm = 0.002), and in smokers (OR = 1.39, pperm = 0.020). BAG3 rs196329 was associated with lower risk in males (A allele: OR = 0.82, pperm = 0.040), whereas HSPA6 rs753856 was associated with reduced risk in physically active individuals (G allele: OR = 0.61, pperm = 0.008). Additional associations involved clinical or biochemical traits. Functional annotation identified potential regulatory effects, including eQTL associations, overlap with histone marks, and allele-dependent changes in transcription factor binding. HSP70 and BAG variants may contribute to CAD susceptibility and support sex- and lifestyle-informed risk assessment.