Most cited article - PubMed ID 25545672
Apolipoprotein E gene polymorphisms in relation to chronic periodontitis, periodontopathic bacteria, and lipid levels
INTRODUCTION: The pathogenesis of diabetes mellitus (DM) and its complications has been previously linked to elevated levels of interleukin-6 (IL-6); IL-6 triggers intracellular pathways through interaction with the IL-6 receptor (IL-6R). This study aimed to determine the association of single nucleotide polymorphisms (SNPs) IL-6 -597G/A (rs1800797), -572G/C (rs1800796), -174G/C (rs1800795), its receptor (IL-6R) Asp358Ala (+48892A/C, rs2228145) and DM or its complications in the Czech population. MATERIALS AND METHODS: In total, 669 subjects participated in this case-control study, including 167 controls, 119 patients with type 1 DM (T1DM), and 383 patients with type 2 DM (T2DM). The subjects were monitored for glycemia, glycated hemoglobin, lipid profile, glomerular filtration rate (GFR), and common complications, such as diabetic nephropathy (DN), retinopathy (DR), (poly)neuropathy (DPN), and periodontitis (P). RESULTS: Frequencies of the IL-6 and IL-6R alleles or genotypes, and IL-6 haplotypes were similar between the controls and the patients with T1DM or T2DM (P > 0.05). However, lower values of GFR were observed in diabetic patients with IL-6 -174CC homozygotes compared to other (CG and GG) genotypes (P ≤ 0.05). In addition, the IL-6R Asp358Ala variant was associated with DN (P = 0.031, OR = 1.74, 95% CI: 1.05-2.89). After subclassification according to the type of DM, the significant association of the IL-6R polymorphism with DN was only found in T1DM (P = 0.013, OR = 2.90, 95% CI: 1.25-6.71). CONCLUSIONS: This study implies a significant relationship between the IL-6R Asp358Ala polymorphism and DN in Czech T1DM patients.
- Keywords
- Diabetic nephropathy, IL‐6, Polymorphisms,
- MeSH
- Diabetes Mellitus, Type 1 * complications genetics MeSH
- Diabetes Mellitus, Type 2 * complications genetics MeSH
- Diabetic Nephropathies * genetics epidemiology MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Interleukin-6 genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Receptors, Interleukin-6 * genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- IL6 protein, human MeSH Browser
- IL6R protein, human MeSH Browser
- Interleukin-6 MeSH
- Receptors, Interleukin-6 * MeSH
Periodontitis, an inflammatory disease caused by subgingival Gram-negative (G-) bacteria, is linked with loss of the connective tissue and destruction of the alveolar bone. In the regulation of inflammatory response, chemokine receptor 2 (CXCR2), a specific receptor for interleukin-8 and neutrophil chemoattractant, plays an important role. The first aim of this study was to investigate the CXCR2 gene variability in chronic periodontitis (CP) patients and healthy nonperiodontitis controls in the Czech population. The second aim was to find a relation between CXCR2 gene variants and the presence of periodontal bacteria. A total of 500 unrelated subjects participated in this case-control study. 329 CP patients and 171 healthy nonperiodontitis controls were analyzed using polymerase chain reaction techniques for three single-nucleotide polymorphisms (SNPs): +785C/T (rs2230054), +1208T/C (rs1126579), and +1440A/G (rs1126580). A DNA microarray detection kit was used for the investigation of the subgingival bacterial colonization, in a subgroup of CP subjects (N = 162). No significant differences in allele, genotype, haplotype, or haplogenotype frequencies of CXCR2 gene variants between patients with CP and healthy controls (P > 0.05) were determined. Nevertheless, Aggregatibacter actinomycetemcomitans was detected more frequently in men positive for the C allele of the CXCR2 +785C/T polymorphism (61.8% vs. 41.1%, P < 0.05; OR = 2.31, 95% CI = 1.03-5.20) and for the T allele of the CXCR2 +1208C/T variant (61.8% vs. 38.9%, P < 0.05; OR = 2.54, 95% CI = 1.13-5.71). In contrast, no statistically significant associations of CXCR2 variants with seven selected periodontal bacteria were found in women. Although none of the investigated SNPs in the CXCR2 gene was associated with CP, the CXCR2 gene variants can be associated with subgingival colonization of G- bacteria in men with CP in the Czech population.
- MeSH
- Aggregatibacter actinomycetemcomitans pathogenicity MeSH
- Alleles MeSH
- Chronic Periodontitis genetics microbiology MeSH
- Adult MeSH
- Genotype MeSH
- Haplotypes genetics MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Receptors, Interleukin-8B genetics MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- CXCR2 protein, human MeSH Browser
- Receptors, Interleukin-8B MeSH
Chronic periodontitis (CP) and diabetes mellitus (DM) involve several aspects of immune functions, including neutrophil activity and cytokine biology. Considering the critical function of chemokine interleukin-8 (IL-8) in the inflammatory process, the aims of this study were to determine: (i) IL-8 plasma levels; (ii) IL-8 (-251A/T, rs4073) and its receptor 2 (CXCR2, +1208C/T, rs1126579) polymorphisms, and (iii) the presence of the selected periodontal bacteria in types 1 and 2 DM patients (T1DM and T2DM) and systemically healthy controls (HC) with known periodontal status. This case⁻control study comprises of 153 unrelated individuals: 36/44 patients suffering from T1DM+CP/T2DM+CP and 32/41 from HC+CP/non-periodontitis HC. Both the clinical and biochemical parameters were monitored. The genotypes were determined using qPCR, IL-8 plasma levels were measured using an ELISA kit. Subgingival bacterial colonization was analyzed with a DNA microarray detection kit. The IL-8 plasma levels differed significantly between non-periodontitis HC and T1DM+CP/T2DM+CP patients (P < 0.01). Even in HC+CP, IL-8 concentrations were significantly lower than in T1DM+CP/T2DM+CP patients (P ≤ 0.05). No significant associations between the IL-8 plasma levels and the studied IL-8 and CXCR2 polymorphisms or the occurrence of selected periodontal bacteria (P > 0.05) were found. CP does not influence the circulating IL-8 levels. Patients with T1DM+CP/T2DM+CP had higher circulating IL-8 levels than HC+CP/non-periodontitis HC.
- Keywords
- chemokines, chronic periodontitis, diabetes mellitus, interleukin-8, plasma, polymorphism,
- MeSH
- Biomarkers MeSH
- Chronic Periodontitis blood genetics microbiology MeSH
- Diabetes Mellitus, Type 1 blood genetics MeSH
- Diabetes Mellitus, Type 2 blood genetics MeSH
- Adult MeSH
- Genetic Variation MeSH
- Interleukin-8 blood 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
- Names of Substances
- Biomarkers MeSH
- CXCL8 protein, human MeSH Browser
- Interleukin-8 MeSH