RESUMO
OBJECTIVE: Previous studies have suggested that some functional polymorphisms in the matrix metalloproteinase (MMPs) genes are associated with the risk of periodontal disease. However, to date no study has investigated MMP8 gene variants in relation to chronic periodontitis (CP). The aim of this study was to analyse polymorphisms in the MMP8 gene and their associations with microbial composition and clinical manifestation of CP. DESIGN: A total of 619 unrelated Czech subjects were included in the present study. Two polymorphisms [-799C/T (rs11225395) and +17C/G (rs2155052)] in the MMP8 gene were studied in 341 patients with CP and 278 unrelated non-periodontitis controls. Both polymorphisms were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Subgingival bacterial colonisation (occurrence of bacteria in subgingival pockets and gingival sulci) was investigated by a commercial semiquantitative kit in selected subjects (N=169). RESULTS: Our results showed no differences in the allele and genotype frequencies of the MMP8 -799C/T and +17C/G polymorphisms between patients with CP and controls (p>0.05). Nevertheless, the haplotype T(-799)/C(+17) was significantly more frequent in patients with CP than in controls [43.7% vs. 37.6%, p<0.05, OR=1.273 (95% CI: 1.013-1.601)]. Despite significant differences determined in the occurrence of periodontal bacteria between patients with CP and non-periodontitis controls (from p<0.000001 to p<0.05), no significant relationships between periodontal pathogens, MMP8 polymorphisms and CP were found (p>0.05). CONCLUSIONS: Although none of the investigated SNPs in the MMP8 gene was individually associated with periodontitis, specific haplotype showed association with clinical manifestation of chronic periodontitis in a Czech population.
Assuntos
Periodontite Crônica/genética , Gengiva/microbiologia , Haplótipos , Metaloproteinase 8 da Matriz/genética , Polimorfismo Genético , Adulto , Carga Bacteriana , Estudos de Casos e Controles , República Tcheca , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
Genome-wide association studies are providing insight into the genetic basis of common complex diseases: more than 1150 genetic loci [2165 unique single nucleotide polymorphisms (SNPs)] have recently been associated to 159 complex diseases. The hunt for genes contributing to immune-related diseases has been particularly successful in celiac disease, for example, with 27 genome-wide significantly associated loci identified so far. One of the current challenges is how to move from a genetic association with a disease to finding disease-associated genes and causal variants, as a step towards understanding the underlying disease process. About 50% of disease-associated SNPs affect the expression of nearby genes (so-called expression quantitative traits loci or eQTLs) and these can provide clues for finding causal variants. Although eQTLs can be useful, fine mapping and sequencing are required to refine the association signal. Ultimately, sophisticated study designs will be needed to find the causal variants involved in complex diseases. In this review, we use celiac disease as an example to describe the different aspects that need to be considered on the path from genetic association to disease-causing variants.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Doença Celíaca/genética , Regulação da Expressão Gênica/imunologia , Antígenos HLA-DQ/genética , Intestino Delgado/metabolismo , Locos de Características Quantitativas , Linfócitos T CD4-Positivos/imunologia , Doença Celíaca/metabolismo , Doença Celíaca/fisiopatologia , Mapeamento Cromossômico , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Antígenos HLA-DQ/imunologia , Antígenos HLA-DQ/metabolismo , Humanos , Intestino Delgado/imunologia , Intestino Delgado/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Locos de Características Quantitativas/imunologiaRESUMO
BACKGROUND: Interferon gamma (IFN-γ) is one of the key regulatory cytokines that has a significant effect on immune responses. It may be important in the chronic inflammatory diseases such as periodontitis in which increased IFN-γ levels were found. The aim of this study was to analyze +874A/T polymorphism in the IFN-γ gene and its associations with the presence of periodontopathic bacteria and susceptibility to generalized chronic periodontitis (CP). METHODS: A total of 498 unrelated Czech white subjects were included in the present study. Genomic DNA was obtained from the peripheral blood of 244 patients with CP and 254 healthy subjects. The IFN-γ +874A/T polymorphism was determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Subgingival bacterial colonization (A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia, T. denticola, P. micros, F. nucleatum in subgingival pockets) was investigated by the DNA-microarray based periodontal pathogen detection kit in a subgroup of subjects (N=110). RESULTS: Our results showed no differences in the allele and genotype frequencies of the IFN-γ +874A/T polymorphism between patients with CP and controls (P>0.05). Although we found significant differences in the occurrence of periodontal bacteria between patients with CP and healthy controls (from P<0.00001 to P<0.05), no significant association between IFN-γ +874A/T polymorphism and periodontal pathogens was observed in any group. CONCLUSIONS: In conclusion, these findings indicate that putative functional variant in the IFN-γ is not associated with susceptibility to chronic periodontitis or microbial composition in the Czech population.