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Objective: The aim of this study was to replicate associations of GWAS-significant loci with severe COVID-19 in the population of Central Russia, to investigate associations of the SNPs with thromboinflammation parameters, to analyze gene-gene and gene-environmental interactions., Materials and Methods: DNA samples from 798 unrelated Caucasian subjects from Central Russia (199 hospitalized COVID-19 patients and 599 controls with a mild or asymptomatic course of COVID-19) were genotyped using probe-based polymerase chain reaction for 10 GWAS-significant SNPs: rs143334143 CCHCR1 , rs111837807 CCHCR1 , rs17078346 SLC6A20-LLZTFL1 , rs17713054 SLC6A20-LLZTFL1 , rs7949972 ELF5 , rs61882275 ELF5 , rs12585036 ATP11A , rs67579710 THBS3, THBS3-AS1 , rs12610495 DPP9 , rs9636867 IFNAR2 ., Results: SNP rs17713054 SLC6A20-LZTFL1 was associated with increased risk of severe COVID-19 in the entire group (risk allele A, OR = 1.78, 95% CI = 1.22-2.6, p = 0.003), obese individuals (OR = 2.31, 95% CI = 1.52-3.5, p = 0.0002, ( p bonf = 0.0004)), patients with low fruit and vegetable intake (OR = 1.72, 95% CI = 1.15-2.58, p = 0.01, ( p bonf = 0.02)), low physical activity (OR = 1.93, 95% CI = 1.26-2.94, p = 0.0035, ( p bonf = 0.007)), and nonsmokers (OR = 1.65, 95% CI = 1.11-2.46, p = 0.02). This SNP correlated with increased BMI ( p = 0.006) and worsened thrombodynamic parameters (maximum optical density of the formed clot, D ( p = 0.02), delayed appearance of spontaneous clots, Tsp ( p = 0.02), clot size 30 min after coagulation activation, CS ( p = 0.036)). SNP rs17078346 SLC6A20-LZTFL1 was linked with increased BMI ( p = 0.01) and severe COVID-19 in obese individuals (risk allele C, OR = 1.72, 95% CI = 1.15-2.58, p = 0.01, ( p bonf = 0.02)). SNP rs12610495 DPP9 was associated with increased BMI ( p = 0.01), severe COVID-19 in obese patients (risk allele G, OR = 1.48, 95% CI = 1.09-2.01, p = 0.01, ( p bonf = 0.02)), and worsened thrombodynamic parameters (time to the start of clot growth, Tlag ( p = 0.01)). For rs7949972 ELF5 , a protective effect against severe COVID-19 was observed in non-obese patients (effect allele T, OR = 0.67, 95% CI = 0.47-0.95, p = 0.02, ( p bonf = 0.04)), improving thrombodynamic parameters (CS ( p = 0.02), stationary spatial clot growth rates, Vst ( p = 0.02)). Finally, rs12585036 ATP11A exhibited a protective effect against severe COVID-19 in males (protective allele A, OR = 0.51, 95% CI = 0.32-0.83, p = 0.004). SNPs rs67579710 THBS3 , THBS3 - AS1 , rs17713054 SLC6A20-LZTFL1 , rs7949972 ELF5, rs9636867 IFNAR2 -were involved in two or more of the most significant G×G interactions ( p perm ≤ 0.01). The pairwise combination rs67579710 THBS3 , THBS3 - AS1 × rs17713054 SLC6A20-LZTFL1 was a priority in determining susceptibility to severe COVID-19 (it was included in four of the top five most significant SNP-SNP interaction models)., Conclusion: Overall, this study represents a comprehensive molecular-genetic and bioinformatics analysis of the involvement of GWAS-significant loci in the molecular mechanisms of severe COVID-19, gene-gene and gene-environmental interactions, and provides evidence of their relationship with thromboinflammation parameters in patients hospitalized in intensive care units., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Loktionov, Kobzeva, Karpenko, Sergeeva, Orlov and Bushueva.)

Our review seeks to elucidate the current state-of-the-art in studies of 70-kilodalton-weighed heat shock proteins (Hsp70) in neurodegenerative diseases (NDs). The family has already been shown to play a crucial role in pathological aggregation for a wide spectrum of brain pathologies. However, a slender boundary between a big body of fundamental data and its implementation has only recently been crossed. Currently, we are witnessing an anticipated advancement in the domain with dozens of studies published every month. In this review, we briefly summarize scattered results regarding the role of Hsp70 in the most common NDs including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We also bridge translational studies and clinical trials to portray the output for medical practice. Available options to regulate Hsp70 activity in NDs are outlined, too., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Venediktov, Bushueva, Kudryavtseva, Kuzmin, Moiseeva, Baldycheva, Meglinski and Piavchenko.)