Aino Salminen1, Milla Pietiäinen1, Susanna Paju1, Timo Sorsa1, Päivi Mäntylä2,3, Kåre Buhlin1,4, Juha Sinisalo5, Pirkko J Pussinen1. 1. Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 2. Institute of Dentistry, University of Eastern Finland, Kuopio, Finland. 3. Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland. 4. Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden. 5. Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.
Abstract
BACKGROUND: In our recent genome-wide association study, we found that genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum matrix metalloproteinase 8 (MMP-8) concentration and the release of MMP-8 from neutrophils. As MMP-8 is centrally involved in the pathogenesis of periodontitis, we aimed to evaluate the presence of genetic polymorphisms of S100A8/A9/A12, MMP8, and CFH in periodontitis. In addition, we studied whether polymorphisms of these genes affect the concentrations of S100A8, S100A12, MMP-8, or complement activation marker in saliva. METHODS: We genotyped four single-nucleotide polymorphisms (SNPs, rs1560833 in S100A8/A9/A12, rs11225395 in MMP8, rs800292 in CFH, and rs1061170 in CFH) and measured salivary concentrations of S100A8, S100A12, MMP-8, and terminal complement complex (TCC) in the Parogene cohort (n = 508). The cohort was composed of patients with an indication to coronary angiography and all underwent a clinical and radiographic oral examination. RESULTS: CFH polymorphisms rs800292 and rs1061170 were associated with periodontal parameters. None of the polymorphisms showed association with salivary proteins. However, salivary concentrations of S100A8, S100A12, MMP-8, and TCC were strongly associated with the number of periodontal pockets and alveolar bone loss. CONCLUSION: Interestingly, genetic variants of CFH, MMP8, and S100A8/A9/A12 gene regions did not affect salivary levels of measured proteins. However, saliva levels of S100A8, S100A12, MMP-8, and TCC, and CFH polymorphisms were associated with clinical and radiographic signs of periodontitis. Our study further supports the observations that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.
BACKGROUND: In our recent genome-wide association study, we found that genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum matrix metalloproteinase 8 (MMP-8) concentration and the release of MMP-8 from neutrophils. As MMP-8 is centrally involved in the pathogenesis of periodontitis, we aimed to evaluate the presence of genetic polymorphisms of S100A8/A9/A12, MMP8, and CFH in periodontitis. In addition, we studied whether polymorphisms of these genes affect the concentrations of S100A8, S100A12, MMP-8, or complement activation marker in saliva. METHODS: We genotyped four single-nucleotide polymorphisms (SNPs, rs1560833 in S100A8/A9/A12, rs11225395 in MMP8, rs800292 in CFH, and rs1061170 in CFH) and measured salivary concentrations of S100A8, S100A12, MMP-8, and terminal complement complex (TCC) in the Parogene cohort (n = 508). The cohort was composed of patients with an indication to coronary angiography and all underwent a clinical and radiographic oral examination. RESULTS: CFH polymorphisms rs800292 and rs1061170 were associated with periodontal parameters. None of the polymorphisms showed association with salivary proteins. However, salivary concentrations of S100A8, S100A12, MMP-8, and TCC were strongly associated with the number of periodontal pockets and alveolar bone loss. CONCLUSION: Interestingly, genetic variants of CFH, MMP8, and S100A8/A9/A12 gene regions did not affect salivary levels of measured proteins. However, saliva levels of S100A8, S100A12, MMP-8, and TCC, and CFH polymorphisms were associated with clinical and radiographic signs of periodontitis. Our study further supports the observations that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.