Association Study of Candidate Genes for Dental Caries in Adults

Objective: Prevention of caries in adults requires multifactorial approaches including behavior modification and access to oral health care. A better understanding of caries etiologic factors in adults would also allow improved prevention. We hypothesized that there is an important genetic component to adult caries and in this study investigate association with candidate genes.

Methods: COHRA (Center of Oral Health Research in Appalachia) has recruited 494 households of at least one parent-child and collected biological samples. For the genetic analysis of independent adults, we used Pearson chi-square case-control analysis on the 627 genotyped parents (males: n=220,age= 36.8±9.5, DMFT=8.8±5.9, DMFS=19.3±19.4; females: n=407, age=34.0±8.3, DMFT=8.4±5.2, DMFS=18.0±16.3) for association of 28 SNPs in 21 genes with various levels of age-dependent-affection-statuses, and regression to model genes, age, gender, S.mutans and saliva flow as predictors of DMFT and DMFS. The candidate genes were chosen for their association with saliva, taste preference, enamel and mineral interactions.

Results: The G allele (p=0.006 frequency=35%) and the AG genotype (p=0.01) of the MMP2 gene is associated with DMFT³1 versus DMFT=0 and DMFT³4 versus DMFT=0 (p=0.007 p=0.01 respectively).The presence of high levels of S.mutans is associated with DMFT³3 (p<0.0008). Regression analyses show age (p<0.0001), CACNB4 Saliva pathway gene (p=0.09), ENAM1 (p=0.04) and S.mutans (p=0.04) separately and together are predictors explaining 9% in the variation of DMFT. Similar results for DMFS explain 12% of the variance, but a KCNN1 saliva pathway gene is involved rather than CACNBA. In each model, the Saliva pathway genes are protective while S.mutans, ENAM1 and age are contributory; interactions are unimportant.

Conclusions: A model including S.mutans levels as well as saliva pathway genotypes best predicted both DMFT and DMFS in adults. These results help explain individual differences in oral health in adults who share comparable environment, diet, and access to dental care.

NIH Grant#R01-DE014889