Most cited article - PubMed ID 15025214
Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis
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
BACKGROUND: Glutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population. METHODS: We analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr). RESULTS: The GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively). CONCLUSIONS: This study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.
- Keywords
- GSTs, Gene, Glutathione S-transferase, Periodontitis, Polymorphism,
- MeSH
- Genetic Predisposition to Disease * genetics MeSH
- Genotype MeSH
- Glutathione Transferase * genetics MeSH
- Humans MeSH
- Polymerase Chain Reaction MeSH
- Risk Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- glutathione S-transferase M1 MeSH Browser
- glutathione S-transferase T1 MeSH Browser
- Glutathione Transferase * MeSH
- GSTP1 protein, human MeSH Browser
Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‑10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‑10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.
- Keywords
- aggressive periodontitis, genetic predisposition, inflammation, interleukin, oral bacteria, polymorphism,
- MeSH
- Aggressive Periodontitis genetics immunology microbiology MeSH
- Alleles MeSH
- Bacteria genetics MeSH
- Adult MeSH
- Gene Frequency genetics MeSH
- Genetic Predisposition to Disease genetics MeSH
- Genotype MeSH
- Haplotypes genetics MeSH
- Interleukin-1 genetics MeSH
- Interleukin-10 genetics MeSH
- Interleukin-17 genetics MeSH
- Interleukin-18 genetics MeSH
- Interleukin-6 genetics MeSH
- Interleukins genetics metabolism MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Periodontitis genetics immunology MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Interleukin-1 MeSH
- Interleukin-10 MeSH
- Interleukin-17 MeSH
- Interleukin-18 MeSH
- Interleukin-6 MeSH
- Interleukins MeSH
Our 10-year study of early-onset periodontitis (EOP) patients includes repeated clinical observations, microbiological characteristics and analysis of genetic polymorphism of IL-1A and IL-1B genes. Twenty patients (age 15-26 years) were divided according to the clinical status in the 4th year into a group with mean number of teeth with bleeding on probing (BP) 9.8 and mean number of teeth with periodontal pocket (PP) 2.23, and a group with mean number of teeth with BP 5.37 and no PP. Significantly higher values of mean BP and PP were found among the groups during the study but a strong progression of disease was found only in 3 patients. The risk IL-1A allele-2 and IL-1B allele-2 genotype and bacterial presence were analyzed by DNA hybridization methods. No significant differences of bacteria composition (Treponema denticola, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans) were found between the groups. A higher prevalence of composite IL-1 genotype was detected in the group of EOP patients with progressive disease. Early finding of the disease followed by conservative therapy could positively influence the disease progression. EOP treated in early stages may, but need not, develop into the aggressive form in the presence of risk genotype IL-1.
- MeSH
- Aggregatibacter actinomycetemcomitans isolation & purification MeSH
- Bacteria isolation & purification MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Interleukin-1 genetics MeSH
- Humans MeSH
- Urban Population MeSH
- Adolescent MeSH
- Oral Hygiene MeSH
- Periodontal Index MeSH
- Periodontitis diagnosis genetics microbiology prevention & control MeSH
- Polymorphism, Genetic MeSH
- Porphyromonas gingivalis isolation & purification MeSH
- Prevotella intermedia isolation & purification MeSH
- Treponema denticola isolation & purification MeSH
- Dental Health Surveys MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Interleukin-1 MeSH