An Interleukin-1β (IL-1β) Single-Nucleotide Polymorphism at Position 3954 and Red Complex Periodontopathogens Independently and Additively Modulate the Levels of IL-1β in Diseased Periodontal Tissues

Inflammatory cytokines such as interleukin-1 (IL-1) are involved in the pathogenesis of periodontal diseases. A high individual variation in the levels of IL-1 mRNA has been verified, which is possibly determined by genetic polymorphisms and/or by the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans .I n this study, we investigated the role of an IL-1 promoter single-nucleotide polymorphism at position 3954 [IL-1(3954) SNP] and the presence of the periodontopathogens in the determination of the IL-1 levels in the periodontal tissues of nonsmoking chronic periodontitis (CP) patients (n 117) and control (C) subjects (n 175) and the possible correlations with the clinical parameters of the disease. IL-1(3954) SNP was investigated by restriction fragment length polymorphism, while the IL-1 levels and the presence of the periodontopathogens were determined by real-time PCR. Similar frequencies of IL1(3954) SNP were found in the C and CP groups, in spite of a trend toward a higher incidence of T alleles in the CP group. The IL-1(3954) SNP CT and TT genotypes, as well as P. gingivalis, T. forsythia, and T. denticola, were associated with higher IL-1 levels and with higher values of the clinical parameters of disease severity. Concomitant analyses demonstrate that IL-1(3954) and the red complex periodontopathogens were found to independently and additively modulate the levels of IL-1 in periodontal tissues. Similarly, the concurrent presence of both factors was associated with increased scores of disease severity. IL-1(3954) genotypes and red complex periodontopathogens, individually and additively, modulate the levels of IL-1 in the diseased tissues of nonsmoking CP patients and, consequently, are potentially involved in the determination of the disease outcome. Periodontal diseases are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that are thought to determine the clinical outcome of the disease (26). The presence of periodontopathogens, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans, considered the major etiologic agents in periodontitis (8), triggers the expression of proinflammatory cytokines, such as interleukin-1 (IL-1), which have been associated with the immunopathology of periodontitis (14). IL-1 has been particularly studied as a critical determinant of tissue destruction due to its proinflammatory and bone resorptive properties, and indeed, increased levels of IL-1 in gingival crevicular fluid were correlated with the severity of periodontal disease (13, 16, 54). Interestingly, variation in cytokine levels among periodonti