Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial asthma alone was found to be associated with rs1927914 ( TLR4 ), rs1928298 (intergenic variant), and rs1980616 ( SERPINA1 ); hypertension alone was found to be associated with rs11065987 (intergenic variant); rs2284033 ( IL2RB ), rs11191582 ( NT5C2 ), and rs11669386 ( CARD8 ); comorbidity between asthma and hypertension was found to be associated with rs1010461 ( ANG/RNASE4 ), rs7038716, rs7026297 ( LOC105376244 ), rs7025144 (intergenic variant), and rs2022318 (intergenic variant). The results suggest that genetic background of comorbidity of asthma and hypertension is different from genetic backgrounds of both diseases manifesting isolated.

Linkage disequilibrium (LD) of single nucleotide polymorphisms (SNPs) of TLR4/AL160272.2 (rs1927914, rs1928298, rs7038716, rs7026297, rs7025144) was estimated in the Slavs of West Siberia. We further investigated an association of SNPs in TLR4/AL160272.2 (rs1927914, rs7038716, rs7025144), SERPINA1 (rs1980616), ATXN2/BRAP (rs11065987), IL2RB (rs2284033), NT5C2 (rs11191582), CARD8 (rs11669386), ANG/RNASE4 (rs1010461), and ABTB2/ САТ (rs2022318) genes with bronchial asthma (BA), arterial hypertension (AH) and their comorbidity. Then, the disease-associated SNPs were annotated in silico in relation to their potential regulatory functions. Strong LD was detected between rs1928298 and rs1927914, as well as rs7026297 and rs7038716 in the Slavs of West Siberia. It was found that the rs1927914 G allele of the TLR4 gene and the rs1980616 C allele of the SERPINA1 gene are associated with the predisposition to BA. These SNPs can affect binding affinity of transcription factors of the Pou and Klf4 families, as well as the expression levels of the TLR4 and SERPINA1 genes. The rs11065987 allele A of the ATXN2/BRAP genes, the rs11669386 A allele of the CARD8 gene, the rs2284033 allele G of the IL2RB gene, and the rs11191582 allele G of the NT5C2 gene were associated with the risk of AH. These variants can alter binding affinity of the Hoxa9, Irf, RORalpha1 and HMG-IY transcription factors, as well as the expression levels of the ALDH2, CARD8, NT5C2, ARL3, and SFXN2 genes in blood cells/vessels/heart, respectively. The risk of developing a comorbid phenotype of AD and AH is associated with the A allele of rs7038716 and the T allele of rs7025144 of the TLR4/AL160272.2 genes, the A allele of rs1010461 of the ANG gene and the C allele of rs2022318 of the ABTB2/CAT genes. Variants rs7038716 and rs7025144 can change the expression levels of the TLR4 gene in blood cells, while rs1010461 and rs2022318 influence the expression levels of the ANG and RNASE4 genes as well as the CAT and ABTB2 genes in blood cells, lungs/vessels/heart.

The ATOX1 (Antioxidant Protein 1) is a human copper metal chaperone that plays an important role in cellular copper homeostasis. The protein is responsible for cytosolic copper absorption from CTR1 (copper transporter 1) and transport to the copper pumps in the Trans Golgi network to the ATP7A and ATP7B proteins. This review collects data on the antioxidant role of ATOX1, the gene role’s in the angiogenesis regulation and cancer cell proliferation, and its role in the pathogenesis of copper-induced diseases—Wilson–Konovalov disease and Menkes disease.

Osteogenesis imperfecta (OI) is a group of connective tissue disorders with different types of inheritance. OI is characterized by bone fragility and deformities, frequent fractures, low bone-mineral density, and impaired bone micro-architectonics. We described here a case of a one-year-old Tuvan patient with multiple fractures. The disease manifestation occurred first at 12 weeks of age as a shoulder joint bruise, and during the year, the patient sustained 27 fractures. Genetic testing revealed a novel homozygous mutation, c.259_260insCGGCC (p.T87fs), in the SERPINF1 gene. This insertion leads to an open-reading frameshift, and the mutation is not represented in the databases. Mutations in SERPINF1 lead to type VI OI, the clinical picture of which is similar to the disease phenotype manifestation of the patient. Thus, the patient’s diagnosis was established by finding a novel pathogenic variant in the SERPINF1 gene.

Rafiq syndrome (RAFQS) is a congenital disorder of glycosylation (CDG) that is caused by mutations in the MAN1B1 gene and characterized by impaired protein and lipid glycosylation. RAFQS is characterized by a delay in intellectual and motor development, facial and other dysmorphism, truncal obesity, behavior problems, and hypotonia. We describe a Russian patient with delayed intellectual and motor development, a lack of speech, disorientation in space and time, impaired attention and memory, and episodes of aggression. Screening for lysosomal, amino acid, organic acid, and mitochondrial disorders was normal. The patient was referred for the targeted sequencing of the “Hereditary Metabolic Disorders” panel. The genetic testing revealed two heterozygous pathogenic variants in the MAN1B1 gene: the previously reported c.1000C > T (p.Arg334Cys) and the novel c.1065 + 1 G > C. Thus, the patient’s clinical picture and genetic analysis confirmed RAFQS in the patient.

Hypertension, coronary heart disease, myocardial infarction, obesity, and type 2 diabetes mellitus are common comorbidities in patients with bronchial asthma. The causes for developing these diseases are multifactorial and involve inherited genetic factors. However, little is known about the genes contributing to the development of comorbidities in bronchial asthma and cardiovascular disease continuum.Objective. To examine the associations of genetic polymorphic variants potentially involved in the development of bronchial asthma comorbid with hypertension, coronary heart disease, type 2 diabetes mellitus, and obesity.Material and Methods. Genotyping of 92 single nucleotide polymorphisms (SNPs) was performed using MALDI-TOF mass spectrometry in patients with bronchial asthma associated with cardiovascular/metabolic disorders (n = 162) compared with a control group of apparently healthy individuals (n = 153).Results. The development of bronchial asthma phenotypes comorbid with cardiovascular/metabolic disorders was associated with the particular genetic variants affecting the expression of genes including CAT, TLR4, ELF5, ABTB2, UTP25, TRAF3IP3, NFKB1, LOC105377347, C1orf74, IRF6, and others in the target organs of study disease profile. Only one SNP (rs11590807), which is regulatory for the UTP25, IRF6, TRAF3IP3, and RP1-28O10.1 genes, was associated with all studied comorbid phenotypes of bronchial asthma and diseases of cardiovascular continuum.Conclusion. The obtained results demonstrated that the identified SNPs affecting the expression of many genes may serve as potential biological markers of complex causal relationships between bronchial asthma and cardiometabolic disorders.