Exploring the genetic basis of chronic periodontitis: a genome-wide association study.

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10(-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28-1.73, P = 3.5 × 10(-7)))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24-1.59, P = 7.5 × 10(-8)), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52-2.65, P = 8.2 × 10(-7)). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10(-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.

Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population.

OBJECTIVES: To study the levels of systemic markers for inflammation with parameters of periodontal diseases in older people. DESIGN: A cross-sectional study was conducted in a cohort that is being followed prospectively on the effects of aging and body composition on morbidity. SETTING: University of Pittsburgh, Pittsburgh, and University of Tennessee, Memphis. PARTICIPANTS: One thousand one hundred thirty-one participants (mean age+/-standard deviation 72.7+/-2.8); 66% white and 50% male. MEASUREMENTS: Periodontal examination, including probing depth and attachment loss, was performed. Periodontal disease extent was divided into 0% of sites with probing depth of 6 mm or more, 1% to 10% of sites with probing depth of 6 mm or more and more than 10% of sites with probing depth of 6 mm or more. Subgingival plaque samples were collected from four molar teeth, and the levels of periodontal pathogens were determined using the benzoyl-DL-arginine-naphthylamide (BANA) test. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), and tumor necrosis factor alpha (TNF-alpha) levels were measured in all participants. Assessments of risk factors associated with elevated levels of markers of systemic inflammation were also determined. Multiple regression analysis was employed to analyze the data. RESULTS: IL-6 levels were significantly higher in participants with more-extensive periodontal disease than in other participants. Periodontal disease extent was significantly associated with higher TNF-alpha plasma levels, controlling for established risk factors for elevated TNF-alpha levels. Participants with BANA-positive species had significantly higher CRP plasma levels when controlling for risk factors for elevated CRP levels. CONCLUSION: Periodontal disease and infection may be modifiable risk indicators for elevated levels of systemic inflammatory markers in older people.

Periodontitis and airway obstruction.

BACKGROUND: The objective of this study was to examine the relationship between airway obstruction and periodontal disease. METHODS: Participants were a subset of 860 community- dwelling, well functioning elderly (aged 70 to 79, blacks and whites, males and females) selected from 2,732 participants enrolled in the Health, Aging, and Body Composition Study (Health ABC). The periodontal evaluations occurred over years 2 and 3 of the study and included four indices of periodontal health: plaque index (PI), gingival index (GI), probing depth (PD), and loss of attachment (LOA). The pulmonary evaluation took place in year 1: conducted according to American Thoracic Society criteria, based on the forced expiratory volume/forced vital capacity (FEV1/FVC) ratio and then using the percent of predicted FEV1 to categorize severity. RESULTS: GI (P = 0.023) and LOA (P = 0.009) were significantly better in participants with normal pulmonary function compared to those with airway obstruction after adjusting for age, race, gender, and field center. When stratified by smoking status and after adjusting for age, race, gender, center, and pack-years, there was a significant association between periodontal health and airway obstruction in former smokers. Within this group, those with normal pulmonary function had significantly better GI (P = 0.036) and LOA (P = 0.0003) scores than those with airway obstruction. All periodontal indices were elevated in smokers regardless of pulmonary status; however, the current smoker group was too small to detect a periodontitis effect. CONCLUSION: While the present cross-sectional study cannot provide direct inference of cause and effect, it does reveal a significant association between periodontal disease and airway obstruction, particularly in former smokers.

Edentulism and nutritional status in a biracial sample of well-functioning, community-dwelling elderly: the health, aging, and body composition study.

BACKGROUND: Edentulism may affect dietary intake in older adults, but the relation between edentulism and nutritional status is not completely understood. OBJECTIVE: The present study examined whether edentulism is associated with nutritional status and whether there is an interaction between race and edentulism on nutritional status among well-functioning, community-dwelling elderly. DESIGN: The study cohort included 3075 elderly aged 70-79 y (52% women, 42% black) in the Health, Aging, and Body Composition Study. Dietary intake, anthropometric variables, weight change, and serum albumin and lipid concentrations were compared between edentate and dentate participants by the use of multiple linear and logistic regressions. RESULTS: Edentulism was not associated with total energy or food intake but was associated with the food groups consumed, particularly fat, micronutrients, and hard-to-chew foods. Edentulism was more strongly linked to dietary intake in whites than in blacks. Unlike black edentate elderly, white edentate elderly consumed significantly lower energy-adjusted amounts of vitamin A and beta-carotene, higher amounts of energy-adjusted total and saturated fat and cholesterol, and higher percentages of energy from fat than did white dentate elderly. Anthropometry and biochemical indexes were not significantly different by edentulism status in both races. Edentulism was associated with weight gains of >5% in 1 y in both races. CONCLUSIONS: Edentulism was associated with differences in the nutritional status of well-functioning, community-dwelling elderly, more so in whites than blacks. Edentate elders may benefit from dental, medical, and nutrition interventions targeted to addressing these findings.

Periodontal disease and weight loss in older adults.

OBJECTIVES: To determine the association between periodontal disease and weight loss in an elderly cohort. DESIGN: A longitudinal design was used with participants from the Health, Aging and Body Composition (Health ABC) cohort study to determine the association between periodontal disease status and weight loss of at least 5% of baseline body weight over a period of 2 years. SETTING: Participants were examined in research clinics in Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A randomly selected subset of 1,053 individuals from the Health ABC examination, aged 65 and older, ambulatory and community-dwelling at baseline. MEASUREMENTS: Periodontal disease was measured as mean pocket depth and attachment loss, extent (percentage) of pockets with at least 6 mm probing depth, extent of bleeding on probing, and tissue inflammation. RESULTS: In logistic regression models adjusting for variables that may explain weight loss, extent of periodontal pockets with at least 6 mm probing depth showed a significant association with weight loss (odds ratio=1.53, 95% confidence interval=1.32-1.77). CONCLUSION: Periodontal disease may be causally related to weight loss in the elderly and thus may increase risk of morbidity and mortality.

Adverse oral health and cognitive decline: the health, aging and body composition study.

OBJECTIVES: To investigate the relationship between periodontal disease and cognitive decline. DESIGN: Analysis of a prospective cohort study. SETTING: The Health, Aging and Body Composition (Health ABC) Study. PARTICIPANTS: One thousand fifty-three participants who were administered the Modified Mini-Mental State Examination (3MS) at Year 1 (baseline) and Year 3 and had participated in a comprehensive periodontal examination at Year 2. MEASUREMENTS: The prospective association between a range of oral health parameters and cognitive function was examined. Decline in 3MS score from Year 3 to 5 was investigated in 947 (89.9%) participants. Covariates included age, sex, education, race, cardiovascular disease and risk, and depressive symptoms. RESULTS: Most indicators of adverse oral health at Year 2 were associated with cognitive impairment based on averaged 3MS scores less than 80 for Years 1 and 3, but education and race substantially confounded these associations. Higher gingival index, a measure of gingival inflammation, at Year 2 remained independently associated with this definition of cognitive impairment and, in fully adjusted analyses, was also an independent predictor of a more-than-5-point cognitive decline from Year 3 to 5. CONCLUSION: Periodontitis may be a risk factor for cognitive decline. Gingivitis is reversible, and periodontitis to some degree is preventable and controllable when manifest. Therefore, further research is needed to clarify potential underlying mechanisms and oral health interventions that might ameliorate cognitive decline.

Modifiable risk factors for pneumonia requiring hospitalization of community-dwelling older adults: the Health, Aging, and Body Composition Study.

OBJECTIVES: To identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization of community-dwelling older adults. DESIGN: Prospective observational cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Of 3,075 well-functioning community-dwelling adults aged 70 to 79 enrolled in the Health, Aging, and Body Composition Study from 1997 to 1998, 1,441 had complete data in the data set of all variables used, a dental examination within 6 months of baseline, and were eligible for this study. MEASUREMENTS: The primary outcome was pneumonia requiring hospitalization through 2008. RESULTS: Of 1,441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male sex (hazard ratio (HR) = 2.07, 95% confidence interval (CI) = 1.51-2.83), white race (HR = 1.44, 95% CI = 1.03-2.01), history of pneumonia (HR = 3.09, 95% CI = 1.86-5.14), pack-years of smoking (HR = 1.006, 95% CI = 1.001-1.011), and percentage of predicted forced expiratory volume in 1 minute (moderate vs mild lung disease or normal lung function, HR = 1.78, 95% CI = 1.28-2.48; severe lung disease vs mild lung disease or normal lung function, HR = 2.90, 95% CI = 1.51-5.57) were nonmodifiable risk factors for pneumonia. Incident mobility limitation (HR = 1.77, 95% CI = 1.32-2.38) and higher mean oral plaque score (HR = 1.29, 95% CI = 1.02-1.64) were modifiable risk factors for pneumonia. Average attributable fractions revealed that 11.5% of cases of pneumonia were attributed to incident mobility limitation and 10.3% to a mean oral plaque score of 1 or greater. CONCLUSION: Incident mobility limitation and higher mean oral plaque score were two modifiable risk factors that 22% of pneumonia requiring hospitalization could be attributed to. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults.

Periodontitis and Airway Obstruction.

BACKGROUND: The objective of this study was to examine the relationship between airway obstruction and periodontal disease. METHODS: Participants were a subset of 860 community- dwelling, well functioning elderly (aged 70 to 79, blacks and whites, males and females) selected from 2,732 participants enrolled in the Health, Aging, and Body Composition Study (Health ABC). The periodontal evaluations occurred over years 2 and 3 of the study and included four indices of periodontal health: plaque index (PI), gingival index (GI), probing depth (PD), and loss of attachment (LOA). The pulmonary evaluation took place in year 1: conducted according to American Thoracic Society criteria, based on the forced expiratory volume/forced vital capacity (FEV1 /FVC) ratio and then using the percent of predicted FEV1 to categorize severity. RESULTS: GI (P = 0.023) and LOA (P = 0.009) were significantly better in participants with normal pulmonary function compared to those with airway obstruction after adjusting for age, race, gender, and field center. When stratified by smoking status and after adjusting for age, race, gender, center, and pack-years, there was a significant association between periodontal health and airway obstruction in former smokers. Within this group, those with normal pulmonary function had significantly better GI (P = 0.036) and LOA (P = 0.0003) scores than those with airway obstruction. All periodontal indices were elevated in smokers regardless of pulmonary status; however, the current smoker group was too small to detect a periodontitis effect. CONCLUSION: While the present cross-sectional study cannot provide direct inference of cause and effect, it does reveal a significant association between periodontal disease and airway obstruction, particularly in former smokers.