# The Role of Epigenetics in Periodontal and Systemic Diseases and Smoking: A Systematic Review
## 3 Results
### Characteristics of the Outcomes Measured
#### 3.7.1 Individual Study Outcomes  
DNA Methylation of Candidate Genes  
Methylation of candidate genes in periodontitis and metabolic disorder. [PERSON] et al. (2016) evaluated the DNA methylation status of _CXCL12_ in buccal mucosa epithelial cells from patients with CP, compared to diabetes with CP patients (D/P) and healthy controls [34]. The authors reported that the _CXCL12_ promoter was predominantly unmethylated in all groups. However, both the CP and D/P groups had increased frequency and percent methylation of the _CXCL12_ promoter compared to healthy controls, albeit no statistically significant difference [34]. Methylation of candidate genes in periodontitis and rheumatoid arthritis. [PERSON] et al. (2012) evaluated the DNA methylation status of 19 IL6 CpG motifs in the peripheral blood from patients with CP compared to RA and controls [36]. The authors found that the methylation levels at the CpG motif at \(-74\ bp\) and \(+19\ bp\) were significantly lower in patients with CP and RA compared to controls; the methylation levels at \(-74\ bp\), but not \(+19\ bp\), were also associated with serum _IL6_ and _IL6_ production by mono-nuclear cells, and the other 17 CpG motifs exhibited comparable methylation levels between groups [36]. [PERSON] et al. (2016) evaluated the DNA methylation status of 12 CpG motifs in the _TNF_ gene promoter region in peripheral blood from participants with CP compared to RA and controls [35]. The authors reported that both the CP and RA groups showed significantly higher methylation rates and frequencies than the control groups at \(-72\ bp\), and the RA group additionally exhibited significantly higher methylation rates and/or frequencies at 6 additional CpG motifs compared to controls. The levels of _TNF_ produced were significantly different between individuals with and without methylation at \(-163\ bp\) (significantly higher hypermethylation rate and frequency in the RA group) [35]. Methylation of candidate genes in periodontitis and cancer. [PERSON] et al. (2010) observed the hypermethylation status of _E-cadherin_ and _COX2_ genes in blood samples and gingival tissues in CP patients compared to neoplastic tissues from breast cancer patients and blood samples from healthy controls [39]. The authors reported hypermethylation of candidate genes in both CP and cancer groups, with higher methylation frequencies in the cancer patients compared to CP patients and _E-cadherin_ methylation compared to _COX2_ gene methylation [39]. [PERSON] et al. (2014) analyzed the methylation status of _TIMP1_, _GSTP1_, _14-3-\(3\sigma\)_ genes in peripheral blood and gingival tissues from periodontitis patients compared to neoplastic tissues from breast cancer patients and blood samples from healthy controls [38]. The authors reported that the hypermethylation frequencies of _TIM-3_ and _GSTP1_ were similar in the periodontitis and control groups, but both were significantly lower than those for malignant disease patients. The methylation frequency of _14-3-\(3\sigma\)_ periodontitis was significantly higher than in the cancer and control groups [38]. [PERSON] et al. (2016) profiled the DNA methylome of gingival tissue from CP patients, compared to oral squamous cell carcinoma samples (OSCC) and healthy controls [37]. The authors observed significant overlap between the altered DNA methylation patterns in CP and OSCC; specifically, the authors reported that for _SOCS1_ and _RMI2_, hypermethylated CpG sites in CP were also hypermethylated in OSCC, and hypomethylated CpG sites in CP were also hypomethylated in OSCC [37]. Methylation of candidate genes in periodontitis and smokers/non-smokers. [PERSON] et al. (2009) analyzed the DNA methylation status of the CXCL8 gene promotor region in epithelial oral mucosa cells from CP smokers, CP non-smokers, and non-periodontitis non-smokers [42]. The authors reported that independent of smoking status, the CP group had higher percentages of hypomethylation and higher expression of _CXCL8_ mRNA than non-periodontitis non-smoker controls.