Oxidative stress may play a role in the recurrent miscarriage (RM) with no known etiology. This study was conducted to investigate the association of polymorphisms in oxidative stress-related genes with idiopathic RM. A total of 331 idiopathic RM patients and 197 controls were genotyped for ABCB1 rs1045642, CYP1A1 rs1048943 and rs4646903, COMT rs4680, CAT rs17880664, GCLC rs17883901, GPX4 rs713041, NRF2 rs6721961, SOD2 rs4880, and OGG1 rs1052133. A protective effect of COMT rs4680-G allele on RM was shown in individual SNP analysis: P = 0.0016, OR = 0.47, 95% CI 0.29–0.75. The multi-factor dimensionality reduction (MDR) approach revealed gene–gene interactions for ABCB1, COMT, GPX4, and OGG1 genes. Cumulative gene risk score analysis demonstrated that more than three risk alleles in the genes ABCB1 (rs1045642-T), COMT (rs4680-A), GPX4 (rs713041-T), and OGG1 (rs1052133-G) were associated with idiopathic RM P = 1.2 × 10^{− 3}, OR = 1.97, 95% CI 1.31–2.97. In silico data interpreting by GeneMANIA analysis revealed genetic, physical, pathway, and coexpression networks for these four genes.

The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.

Results of expression studies can be useful to clarify the genotype-phenotype relationship. However, according to data from recent literature, there is a large group of genes that are revealed as differentially expressed (DE) in many studies, regardless of the biological context. Additional analyses could shed more light on the relationships between genes, their differential expression, and diseases. We generated a set of 9972 disease genes from five gene-phenotype databases (OMIM, ORPHANET, DDG2P, DisGeNet and MalaCards) and a report of the International Union of Immunological Societies. To study transcriptomics of disease and non-disease genes in healthy tissues, we obtained data from the Human Protein Atlas (HPA) website. We analyzed the dependency between expression in healthy tissues and gene occurrence in Gene Expression Omnibus series using tools within the Enrichr libraries. The results of expression studies were annotated with Gene Ontology (GO) and Human Phenotype Ontology (HPO) terms. Using transcriptomics analysis of healthy tissues, we validated the previous findings of higher expression levels of disease genes in pathologically linked tissues compared to other tissues. Preferentially DE genes were generally highly expressed in one or multiple tissues and were enriched for disease genes. According to the results of GO enrichment analyses, both down- and up-regulated DE genes most often took part in immune response, translation and tissue-specific processes. A connection between DE-related pathology and the diversity of HPO terms was found. Investigating a link between expression and phenotype contributes to understanding the mode of development and progression of human diseases.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R² = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.