ABSTRACT
AIM: The indispensable role of interleukin-6 receptor (IL-6R) in regulating IL-6 responses has been clearly established. We have previously reported that IL6R polymorphisms strongly influenced the serum levels of soluble IL-6R. In this study, we investigated the association between these genetic variations and periodontitis. MATERIAL AND METHODS: Among the seven novel IL6R single-nucleotide polymorphisms (SNPs) reported, we genotyped two important sites: the +48892 A/C in exon 9 and the -183 G/A in the promoter region. The SNP in exon 9 results in Asp-->Ala substitution in the proteolytic cleavage site of IL-6Ralpha. In total, 212 periodontitis cases and 210 healthy controls were genotyped using polymerase chain reaction, restriction fragment length polymorphisms and direct sequencing methods. RESULTS: Analysis of the genotype distribution of the +48892 A/C SNP in periodontitis patients and in controls revealed a suggestive association with aggressive (p = 0.04) and chronic periodontitis (p = 0.04). In addition, the carriage rate for the A allele was significantly higher in chronic periodontitis patients [p = 0.02, odds ratio (OR) = 2.25]. No association was found in the -183 G/A SNP. The two markers were in linkage disequilibrium (LD) (|D'| = 0.53). CONCLUSION: The IL6R+48892 A/C polymorphism could act as a risk factor for periodontitis; however, further association and biological studies are needed.
Subject(s)
Periodontitis/immunology , Polymorphism, Genetic/genetics , Receptors, Interleukin-6/genetics , Adenine , Adult , Aged , Alanine/genetics , Alleles , Aspartic Acid/genetics , Biomarkers/analysis , Cytosine , Exons/genetics , Female , Genetic Variation/genetics , Genotype , Humans , Japan , Linkage Disequilibrium/genetics , Male , Middle Aged , Periodontitis/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/geneticsABSTRACT
BACKGROUND: Soluble types of tumour necrosis factor (TNF) receptors type 1 and 2 modulate the TNF-alpha-mediated inflammatory responses in chronic periodontitis (CP). OBJECTIVES: This study investigated the levels of TNF-alpha, soluble TNF receptor type 1 and 2 in gingival crevicular fluid (GCF) and serum of healthy subjects and CP patients. MATERIALS AND METHODS: Thirty-eight sera and 73 GCF samples were collected from 16 healthy subjects and 22 CP patients. GCF was collected from probing pocket depth (PPD)< or =3 mm sites of healthy subjects, PPD< or =3, 4-6 and > or =7 mm sites of CP patients. The levels of TNF-alpha, soluble TNF receptor type 1 and 2 in the serum and GCF were quantified by enzyme-linked immunosorbant assay. RESULTS: The total amounts of TNF-alpha, soluble TNF receptor type 1 and 2 in GCF significantly elevated with increasing PPD in both site-based (p<0.05) and subject-based (p<0.05) analyses. However, their levels progressively diverged as the pocket depths increased, with the soluble TNF receptor type 2 level being comparatively lower than type 1. On the other hand, soluble TNF receptor type 2/type 1 ratios in GCF decreased as the severity of periodontitis increased (p<0.0001). CONCLUSION: The imbalance between soluble TNF receptor type 1 and 2 levels in GCF could be related to CP severity.
