Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

Periodontal disease is associated with renal insufficiency in the Atherosclerosis Risk In Communities (ARIC) study.

BACKGROUND: Periodontitis, a chronic bacterial infection of the oral cavity, is a novel risk factor for atherosclerotic cardiovascular disease (CVD). Given the numerous shared risk factors for CVD and chronic kidney disease (CKD), we hypothesized that periodontitis also is associated with renal insufficiency in the Dental Atherosclerosis Risk in Communities study. METHODS: We conducted a cross-sectional study of 5,537 middle-aged black and white men and women. Periodontitis was determined by using an independent clinically derived definition and categorized as healthy/gingivitis, initial, and severe. Renal insufficiency is defined as glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 . Multivariable logistic regression models were used to estimate odds ratios and 95% confidence intervals for renal insufficiency using healthy/gingivitis as the referent group. RESULTS: A total of 2,276 individuals had initial periodontitis, and 947 individuals had severe periodontal disease. One hundred ten individuals (2%) had a GFR less than 60 mL/min/1.73 m2 . Compared with healthy/gingivitis, initial and severe periodontal disease were associated with a GFR less than 60 mL/min/1.73 m2 (odds ratio, 2.00; 95% confidence interval, 1.23 to 3.24) for initial periodontal disease and an odds ratio of 2.14 for severe disease (95% confidence interval, 1.19 to 3.85) after adjustment for important risk factors for CVD and CKD. Sensitivity analysis showed that initial and severe periodontitis were each associated with an elevated serum creatinine level (men, >1.4 mg/dL [>124 micromol/L]; women, >1.2 mg/dL [>106 micromol/L]; odds ratio, 3.21; 95% confidence interval, 1.32 to 7.76 and odds ratio, 5.39; 95% confidence interval, 2.08 to 13.99, respectively). CONCLUSION: This is the first study to show an association of periodontal disease with prevalent renal insufficiency. A prospective study is necessary to determine the exact nature of the observed relationship.

Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium.

BACKGROUND: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). METHODS: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49,066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17,672/31,394 with/without periodontitis); 68,761 participants with BMI and genotype data; and 57,871 participants (18,881/38,990 with/without periodontitis) with data on BMI and periodontitis. RESULTS: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. CONCLUSIONS: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.

Clinical and inflammatory evaluation of Perioscopy on patients with chronic periodontitis.

The purpose of this pilot study was to evaluate the clinical and inflammatory changes produced in chronic, non-responsive periodontitis sites when comparing traditional scaling and root planing with scaling and root-planning using Perioscopy The sample size consisted of six patients who exhibited chronic periodontitis after completing initial therapy and under going periodontal maintenance for at least one year. The study was a within patient match site design. In which each patient had six to eight periodontal pockets measuring 5 mm to 8 mm. Half of the sites in each patients mouth were treated with scaling and root planing only (control group) and the other half of the sites were treated with scaling and root planing plus Perioscopy (experimental group). At one month evaluations, 50% of the control sites had a decrease of > 2 mm (11 out of 22 sites) and 55% of the experimental sites had a decrease in pocket depth of > 2 mm (12 out of 22 sites). When comparisons were made between baseline and three month evaluations of total pocket depths, 55% of the control sites had a decrease of > 2 mm (10 out of 22 sites). Chi-Square statistical analysis at one and three month evaluations showed non-significant decreases in pocket depth among control sites and experimental sites (p = 0.76, p = 0.55). At baseline, IL-1 mean levels and control sites were 43.47 pg/ml and 37.29 pg/ml for experimental for one month evaluation. II-1_mean levels were 33.03 pg/ml for control sites and 32.29 pg/ml for experimental sites. At the three month evaluation. IL-1 mean levels were 15.33 pg/ml for control sites and 14.42 pg/ml for experimental sites. Statistical t-test analysis assuming unequal variances at baseline, months one and three showed non-significant trends between control and experimental sites (p = 0.27, p = 0.47, p = 0.45). At baseline, PGE2, levels were 18.85 pg/ml for the control group abd 24,013 pg/ml for experimental sites. At one moth, PGE2 levels were 15.16 pg/ml for control sites and 16.23 pg/ml for experimental sites. At the three month evaluation, PGE2 levels were 14.18 pg/ml for the control sites and 15.92 pg/ml for the experimental group. T-test analysis of unequal variance showed non-significant trends in the data at baseline, one and three months for PGE2 (p = 0.26, p = 0.40, p = 0.31). The intent of this pilot study was to compare the changes in periodontal pocket depths and inflammatory markers of the control (scaling and root planing) and experimental (scaling and root planing with Perioscopy) sites. Analysis revealed no statistically significant differences in clinical and inflammatory analysis of the control sites and experimental sites though the three month evaluation period. Further studies are needed to determine the effectiveness of Perioscopy with a longer evaluation period.

The effect of periodontal therapy on TNF-alpha, IL-6 and metabolic control in type 2 diabetics.

PURPOSE: This pilot study investigated if scaling and root planing (S&RP) was an effective intervention in reducing levels of inflammatory markers TNF-alpha and IL-6 in a type 2 diabetic population. METHODS: Twenty-five patients with type 2 diabetes, 18-64 years of age were enrolled having 4 or more sites with pocket depths > or = 5mm and 2 or more sites with attachment loss > or = 3mm. Participants received S&RP following collection of gingival crevicular fluid and serum which were analyzed for TNF-alpha and IL-6. After 3 months post-treatment levels were collected. Serum pre-and post-treatment levels were analyzed using a paired t test at a significance level of p < or = 0.05. Mean TNF-alpha was 1.7 pg/ml at baseline and post-treatment was 4.0 pg/ml. Mean IL-6 was 2.8 pg/ml at baseline and post-treatment 6.0 pg/ml. RESULTS: Both mean TNF-alpha and IL-6 were increased following S&RP ; however, the observed increases were not statistically significant. While participants improved on periodontal measures following therapy, systemic measures of inflammation (TNF-alpha and IL-6) did not show the hypothesized reductions. CONCLUSION: Further studies are needed to determine effectiveness of S&RP on inflammatory mediators in a population with type 2 diabetes.