A new insight into oxidative stress is based on oxidative deoxyribonucleic acid (DNA) damage. DNA is the pivotal biopolymer for life and health. Arterial hypertension (HT) is a globally common disease and a major risk factor for numerous cardiovascular (CV) conditions and non-cardiac complications, making it a significant health and socio-economic problem. The aetiology of HT is multifactorial. Oxidative stress is the main driver. Oxidative DNA damage (oxidised guanosine (8OHdG), strand breaks (SSBs, DSBs)) seems to be the crucial and initiating causal molecular mechanism leading to HT, acting through oxidative stress and the resulting consequences (inflammation, fibrosis, vascular remodelling, stiffness, thickness, and endothelial dysfunction). In light of the current European Society of Cardiology (ESC) guidelines with defined gaps in the evidence, this manuscript, for the first time, (1) summarizes evidence for oxidative DNA damage in HT and other CV risk factors, (2) incorporates them into the context of known mechanisms in HT genesis, (3) proposes the existing concept of HT genesis innovatively supplemented with oxidative DNA damage, and (4) mentions consequences such as promising new targets for the treatment of HT (DNA damage response (DDR) pathways).

• Keywords
• DDR, DNA damage and strand breaks, ESC guidelines, PARP inhibitors, cardiovascular disease, concept on genesis, heart failure, hypertension, oxidative stress, risk factors and therapy, γH2AX,
• MeSH
• Hypertension * MeSH
• Humans MeSH
• Oxidative Stress * MeSH
• DNA Damage * MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Recent studies have suggested a bidirectional relationship between chronic periodontitis (CP) and diabetes mellitus (DM). Immunoregulatory factors such as cytokines play an important role in etiopathogenesis of both diseases. The aim of this study was to analyze variability in interleukin-1 (IL-1) gene cluster and IL-1β plasma levels in patients with CP, DM, and a combination of both diseases. A total of 1016 individuals participating in this case-control study-225 healthy controls, 264 patients with CP, 132 with type 1 diabetes (T1DM), and 395 patients with type 2 diabetes (T2DM)-were genotyped using methods based on polymerase chain reaction for IL-1 gene polymorphisms (IL-1A (-889C/T, rs1800587), IL-1B (+3953C/T, rs1143634), and IL-1RN (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2)). Levels of IL-1β were measured by Luminex methods in subgroups of controls, CP, T1DM + CP, and T2DM + CP subjects. Although no significant associations were found in the genotype and allele frequencies of IL-1A (-889C/T), significant differences in the allele frequencies of IL-1B (+3953C/T) were observed between controls and CP patients (P < 0.05). In T1DM patients, IL-1RN ∗ S "short" allele and IL-1RN 12 genotype were significantly less frequent than those in controls (P < 0.01). In haplotype analysis, TTL haplotype decreased the risk of CP development (P < 0.01), whereas CCS and CTL haplotypes (P < 0.01 and P < 0.05) were associated with T1DM. Although IL-1β levels were measured significantly higher in mononuclear cells after stimulation by mitogens, HSP70, or selected periodontal bacteria than in unstimulated cells, IL-1 genotypes did not correlate with circulating IL-1β levels. In the Czech population, significant associations between the IL-1B polymorphism with CP and the IL-1RN variant with T1DM were found. Haplotype analysis suggests that variability in IL-1 gene cluster may be one of the factors in the CP and T1DM pathogenesis, although single variants of these polymorphisms are not substantial for protein production.

• Publication type
• Journal Article MeSH

Interleukin-17 contributes to the pathogenesis of type 1 diabetes mellitus (T1DM) and chronic periodontitis (CP). We analyzed IL-17A -197A/G and IL-17F +7488C/T polymorphisms in T1DM and CP and determined their associations with IL-17 production and occurrence of periopathogens. Totally 154 controls, 125 T1DM, and 244 CP patients were genotyped using 5' nuclease TaqMan(®) assays. Bacterial colonization was investigated by a DNA-microarray kit. Production of IL-17 after in vitro stimulation of mononuclear cells by mitogens and bacteria was examined by the Luminex system. Although no differences in the allele/genotype frequencies between patients with CP and T1DM + CP were found, the IL-17A -197 A allele increased the risk of T1DM (P < 0.05). Levels of HbA1c were significantly elevated in carriers of the A allele in T1DM patients (P < 0.05). Production of IL-17 by mononuclear cells of CP patients (unstimulated/stimulated by Porphyromonas gingivalis) was associated with IL-17A A allele (P < 0.05). IL-17A polymorphism increased the number of Tannerella forsythia and Treponema denticola in patients with CP and T1DM + CP, respectively (P < 0.05). IL-17A gene variability may influence control of T1DM and the "red complex" bacteria occurrence in patients with CP and T1DM + CP. Our findings demonstrated the functional relevance of the IL-17A polymorphism with higher IL-17 secretion in individuals with A allele.

• MeSH
• Alleles MeSH
• Chronic Periodontitis blood   genetics   microbiology   MeSH
• Diabetes Mellitus, Type 1 blood   genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genotype MeSH
• Interleukin-17 blood   genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• IL17A protein, human MeSH Browser
• IL17F protein, human MeSH Browser
• Interleukin-17 MeSH