Complement Factor H Polymorphism Associates With MMP-8 Concentration and Periodontitis

Objectives: We recently found in a genome-wide association study that genetic polymorphisms in Complement factor H (CFH) gene and in S100 calcium-binding protein A9 (S100A9) gene region are associated with serum matrix metalloproteinase-8 (MMP-8) concentrations. Moreover, polymorphism in the promoter region of the MMP8 gene is associated with the expression of MMP8. We investigated whether these SNPs are associated with serum or saliva MMP-8 concentrations or periodontitis.
Methods: Three SNPs, rs800292 (CFH Val62Ile variant), rs1560833 (downstream of S100A9 gene), and rs11225395 (in the promoter of MMP8 gene) were genotyped in the Parogene study cohort (n=491) by qPCR. The subjects underwent detailed clinical and radiographic oral examinations. Serum and saliva MMP-8 concentrations were analyzed by IFMA. The association between SNP genotypes, MMP-8 concentrations, and periodontitis were analyzed by linear (for concentrations) and logistic (for periodontitis) regression adjusted for age, gender, smoking, diabetes, and the number of teeth (for saliva MMP-8).
Results: The minor alleles of rs800292 (CFH) and rs1560833 (S100A9) were inversely associated with serum MMP-8 (p=0.003 and p=0.048, respectively), but not with saliva MMP-8. Rs11225395 (MMP8) was not associated with the concentrations of MMP-8 neither in serum nor in saliva. The minor allele of rs800292, causing Val62Ile variation in the CFH protein, was inversely associated with periodontitis (OR 0.67, 95% CI 0.47 – 0.96, p=0.031).
Conclusions: Genetic variations in the CFH gene and S100A9 gene region are associated with serum, but not with saliva MMP-8 levels. The results suggest that different mechanisms contribute to MMP-8 concentrations in the oral cavity and in the systemic circulation. As MMP8 promoter polymorphism was not associated with MMP-8 concentration, it seems that the main regulation mechanism of MMP-8 levels is not the de novo gene expression. The Ile62 variant of CFH was inversely associated with periodontitis, suggesting a role of complement activation in periodontitis.