Common complement factor H polymorphisms are linked with periodontitis in elderly patients

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.

Association of KDR (rs2071559, rs1870377), CFH (rs1061170, rs1410996) genes variants and serum levels with pituitary adenoma

“…The complement molecules modulate systemic inflammatory responses through communication with the pituitary gland (Francis et al, 2003). However, CFH is associated with neurodegenerative diseases, decreased risk of recurrent pregnancy loss, periodontitis, myocardial infarction (MI), and a smoking-related risk factor for lung cancer (Cho et al, 2019;Ezzeldin et al, 2015;Kardys et al, 2007;Maugeri et al, 2019;Salminen et al, 2022;Zhang et al, 2016). A study done by Zhang et al showed that CFH rs1061170 has strong associations with Alzheimer's disease (AD) in the European population and Han Chinese and European populations together (p < 0.001, p meta = 0.0005, respectively) (Zhang et al, 2016) Abbreviations: AIC, akaike information criterion; OR, odds ratio; PA, pituitary adenoma; p-value, significance level (differences considered significant when p < 0.05).…”

DAMPs and alarmin gene expression patterns in aging healthy and diseased mucosal tissues

“…S100A12 was also found to be increased in GCF and serum of CP patients and even more elevated in T2DM patients with periodontitis ( 124 ). S100A8, S100A9, S100A12, were all elevated in saliva from periodontitis and gingivitis patients compared to healthy controls ( 125 ) and salivary levels of S100A8, S100A9 and S100A12 were significantly related to clinical and radiographic signs of periodontitis ( 47 ). The S100A12 gene was a significant DEG in gingival tissues of periodontitis ( 126 ).…”

“…However, evidence provided over the last few decades has emphasized that the tissue destruction in periodontitis most likely is a manifestation of the chronic inflammatory response of the host to the complex microbial challenge that increases in quantity, as well as enabling the emergence of more pathogenic species to stimulate elevated levels of tissue destructive molecules (25,45,46). This view is also supported by ongoing genomic studies suggesting linkages between alterations in inflammatory gene expression and enhanced risk for development of periodontitis (47)(48)(49)(50)(51)(52). Recent investigations have begun to emphasize that this chronic inflammation with tissue destruction is not a unidirectional process.…”

Polymorphisms in Genes Involved in Inflammation and Periodontitis: A Narrative Review

“…Genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum MMP-8 concentration and its release from neutrophils. Salivary concentrations of S100A8, S100A12, MMP-8, terminal complement complex (TCC), and CFG polymorphisms (rs800292 and rs1061170), were strongly associated with the number of periodontal pockets and alveolar bone loss [51]. The authors concluded that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.…”