The genetic impact of the Q551R interleukin-4 receptor alpha polymorphism for aggressive or chronic periodontitis and the occurrence of periodontopathic bacteria.

OBJECTIVE: The Q551R polymorphism of the gene encoded for the α chain of the interleukin-4 receptor (IL-4RA) could influence both IL-4 and IL-13 signalling. Since both cytokines could be important in the pathogenesis of periodontitis the aim of this study was to evaluate putative associations of the Q551R polymorphism to generalized aggressive or chronic periodontitis and five periodontopathogens. DESIGN: 154 patients with severe generalized periodontitis (chronic: n=68, mean age=48.7 ± 9.4 years; aggressive: n=86, mean age=40.4 ± 9.8 years) and controls without periodontitis (n=89, mean age=46.2 ± 10.8 years) were included. The Q551R polymorphism was analysed by PCR-SSP CTS-Kit, Heidelberg, Germany. Subgingival bacteria were determined molecular biologically using micro-Ident test (HainLifescience, Nehren, Germany). Distributions of single alleles and genotypes were calculated by Chi(2)-test with Yates correction or Fisher's exact test. Adjusted odds ratios were generated by logistic regression with respect to established cofactors for periodontitis. RESULTS: The mutant allele R551 (p(Y)=0.013) and the genotypes QR+RR (p(B)=0.024) occurred more frequently amongst patients with chronic periodontitis vs. controls. Carriers of the Q551R polymorphism had an increased adjusted odds ratio for chronic periodontitis (OR=3.2, 95%CI 1.5-6.5, p=0.002) and severe periodontitis (chronic+aggressive) in general (OR=2.0, 95%CI 1.1-3.6, p=0.003). Moreover, in the total study cohort the Q551R polymorphism was associated with the presence of Tannerella forsythia (90.3% vs. 78.0%, p(Y)=0.01). CONCLUSIONS: The Q551R IL-4RA polymorphism is a putative risk indicator for severe chronic periodontitis, but was not significant associated to AP.

Single nucleotide polymorphisms in interleukin-1gene cluster and subgingival colonization with Aggregatibacter actinomycetemcomitans in patients with aggressive periodontitis.

Periodontitis is initiated by the subgingival occurrence of periodontopathogens. It is triggered by a specific host-dependent immune response that is influenced by genetic predisposition. Polymorphisms in the interleukin-1 (IL-1) gene cluster have been suggested to influence the pathogenesis of periodontitis. A total of 159 periodontitis patients (chronic disease: n = 73, aggressive disease: n = 86) and 89 periodontitis-free controls were included in the study. Polymorphisms IL-1α (rs1800587), IL-1ß (rs16944, rs1143634), IL-1 receptor (rs2234650), and IL-1 receptor antagonist (rs315952) were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). Subgingival bacterial colonization was assessed using a polymerase chain reaction/DNA probe test (micro-Ident). Haplotype block structure was determined using Haploview 4.2. Statistical analyses were performed applying SPSS 17.0 considering dominant, recessive, and codominant genetic models. In this case-control study, no association between genomic variants of the IL-1 gene cluster and the incidence of severe periodontitis could be shown. Carriers of the rare genotypes of rs1800587 (p(corr) = 0.009), rs1143634 (p(corr) = 0.009) and composite genotype (rs1800587+rs1143634) (p(corr) = 0.031) had a twofold higher risk for subgingival occurrence of Aggregatibacter actinomycetemcomitans. In forward stepwise binary logistic regression analyses considering age, gender, smoking, and approximal plaque index as potential confounders these significant associations were demonstrated. Despite the genetic background of IL-1 gene cluster could be shown to be associated with subgingival colonization of A actinomycetemcomitans, there is no evidence that it is an independent risk indicator for periodontitis.

Interferon-gamma and interleukin-12 gene polymorphisms and their relation to aggressive and chronic periodontitis and key periodontal pathogens.

BACKGROUND: The gene polymorphisms interferon-gamma (IFN-gamma) 874 T/A and interleukin (IL)-12 1188 A/C have been associated with the altered production of cytokines. Therefore, they might be indicative of the occurrence of chronic periodontitis (CP) or aggressive periodontitis (AgP) and the prevalence of key periodontal pathogens. For this purpose, we analyzed these polymorphisms in subjects with generalized AgP or generalized CP. Moreover, we assessed the relationship between these polymorphisms and five periodontopathic bacteria. METHODS: A total of 124 unrelated German white subjects with periodontitis (AgP=72 and CP=52) and 74 periodontitis-free subjects were studied. Gene polymorphisms were determined by polymerase chain reaction with sequence-specific primers. Subgingival bacteria were molecular biologically analyzed using multiplex polymerase chain reaction and reverse hybridization. The distributions of alleles and genotypes were calculated by the chi(2) test with Yates correction. Risk factor analyses were carried out by logistic regression considering established confounders for periodontitis. RESULTS: Allele and genotype frequencies of both investigated polymorphisms were not significantly different between subjects with periodontitis and periodontitis-free controls. However, in the total study group, IL-12 AA-positive subjects had a significantly higher bleeding index than individuals who expressed IL-12 CC (68.2% versus 50.0%, P=0.025). Moreover, IFN-gamma AA carriers had a decreased odds ratio (OR) for the individual presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) (OR=0.39, P=0.012) after adjustment for age, gender, smoking, and probing depth. IFN-gamma TA predisposed an individual to infection with Prevotella intermedia (OR=2.15, P=0.019). CONCLUSION: Although a relationship between the bleeding index and the presence of bacteria was shown, IFN-gamma and IL-12 polymorphisms are not suitable diagnostic features for AgP and CP.

Genetic markers of tumour necrosis factor alpha in aggressive and chronic periodontitis.

AIM: Tumour necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of periodontitis. TNFalpha production is influenced by gene polymorphisms. The aim of this study was to evaluate links between genetic variants and chronic/aggressive periodontitis in a multivariate model. SUBJECTS: One hundred and twenty-three periodontitis patients (chronic: n=54, aggressive: n=69) and 52 healthy controls without periodontitis were included in the study. MATERIAL AND METHODS: Single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A and haplotypes were analysed by a polymerase chain reaction with sequence-specific primers (PCR-SSP). The clinical investigation included smoking status, plaque and bleeding indexes, pocket depth and attachment loss. RESULTS: Prevotella intermedia occurred more frequently in individuals positive for the -308GG/-238GG haplotype combination (Odds Ratio=2, 95% Confidence interval: 1.1-3.7, p=0.037, 1-beta=61%). In binary logistic regression analyses, this TNFalpha haplotype could not be shown to be associated with periodontitis considering smoking, age, gender and approximal plaque index or subgingival bacterial colonization as confounding factors. CONCLUSIONS: Although the genetic background of TNFalpha could be shown to be associated with subgingival colonization with P. Intermedia, there is no evidence that it is an independent risk factor for periodontitis in multivariate models.