UCSF

Background:

Previous studies have identified several risk factors for periodontal diseases. However, due to many differences between studies (i.e. study design, outcome definitions, and covariates included) the relative importance of these risk factors is unclear. The purpose of this study was to access and compare the magnitude of many known and potential risk factors, and identify the most important risk factors for periodontal diseases.

Methods:

An extensive list of risk factors was investigated with four quantitative outcomes (mean plaque index, percent bleeding on probing, extent pocket depth ≥ 5mm, and extent attachment loss ≥ 3mm) in three elderly populations (Health, Aging, and Body Composition (Health ABC) Study African Americans (n=539), Health ABC Study Caucasians (n=1,010), and Osteoporotic Fractures in Men Study (MrOS) Caucasians (n=686)). Univariate linear regression was used to estimate the percentage of outcome variance accounted for by each risk factor, and backwards stepwise regression was used to estimate the effect sizes associated with the risk factors. We also surveyed the genome for common genetic risk factors by meta-analyzing results from genome-wide association studies in two Caucasian populations (Health ABC Study and MrOS, n=1,373). Significant signals (p≤10^-6) were tested for replication in two elderly populations (Atherosclerosis Risk in Communities Study Caucasians (n=4,165) and Health ABC Study African Americans (n=500)), and in silico analyses were used to evaluate the potential functional importance of the identified genomic regions.

Results:

High plaque levels and inter-examiner effects explained the largest portions of variance of all outcomes. At least half of the variance of each outcome remained unexplained. In meta-analyses, each outcome was found to be associated with variants in one genomic region (p≤10^-6). These signals were not supported by findings from replication studies (p>0.05); however, in silico analyses provided some support for three candidate genes (FBLN1, PTPRT, and PPP2R2B) for future studies.

Conclusion:

Overall, plaque appears to be the largest risk factor for periodontal diseases, compared to any other risk factor or single genetic polymorphism tested in this investigation. No major genetic risk factor was identified, which may suggest these diseases are under the influence of smaller and more complex genetic effects.