Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2

Abstract

Dental caries is a chronic infectious disease that affects billions of people with large individual differences in activity. We investigated whether PRH1 and PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for indigenous bacteria match and predict individual differences in the development of caries. PRH1 and PRH2 variation and adhesion of indigenous and cariogenic (Streptococcus mutans) model bacteria were measured in 452 12-year-old Swedish children along with traditional risk factors and related to caries at baseline and after 5-years. The children grouped into low-to-moderate and high susceptibility phenotypes for caries based on allelic PRH1, PRH2 variation. The low-to-moderate susceptibility children (P1 and P4a-) experienced caries from eating sugar or bad oral hygiene or infection by S. mutans. The high susceptibility P4a (Db, PIF, PRP12) children had more caries despite receiving extra prevention and irrespective of eating sugar or bad oral hygiene or S. mutans-infection. They instead developed 3.9-fold more caries than P1 children from plaque accumulation in general when treated with orthodontic multibrackets; and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion as additional susceptibility traits. The present findings thus suggest genetic autoimmune-like (P4a) and traditional life style (P1) caries, providing a rationale for individualized oral care.

Keywords: Acidic proline-rich proteins; Chronic infections; Dental caries; Host susceptibility; PRH1; PRH2.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Acidic PRP phenotypes, their allelic composition and association with baseline caries. (AB) Allelic types and amounts of mixed acidic PRP phenotypes P1-P10 from gel electrophoresis of parotid saliva in 218 12-year-old children. (C) PLS loading plot showing the association of P4, P6 and P1 children (grey circles) and traditional risk factors (S. mutans, lactobacilli > oral hygiene > sweets >> drinks) with baseline caries in children with Swedish ethnicity (n = 185); Sex = 0 boys, 1 girls; F = extra fluoride; Oh = oral hygiene; WS = whole saliva flow; PS = parotid saliva flow; lbc = lactobacilli in saliva; ms, ms pl, % ms and % ms pl = S. mutans and % of total streptococci in saliva and plaque; strept, strept pl = total streptococcal in saliva, plaque; IBadh = S. mutans adhesion, % and tot; LY7adh = A. oris adhesion, % and tot); Db + etc. and Db etc. = qualitative, +, and quantitative acidic PRP variants from electrophoresis; PRPtot = total amounts of PRPs; P1, P4 etc. = mixed acidic PRP phenotypes from electrophoresis.

Fig. 2

Differential life style risk factor profiles for the high (P4), low (P1) and moderate (P6) phenotypes. PLS loading plots of various factors (left) and influential (VIP) values for selected factors (right) showing their association with caries (DeFS) in P4, P6, and P1 phenotypes (P4 = 40, P6 = 62, P1 = 72 children). Sex = 0 boys, 1 girls; Ethn = ethnicity; F = extra fluoride; Oh = oral hygiene; WS = whole saliva flow; PS = parotid saliva flow; lbc = lactobacilli counts in saliva; ms, ms pl, % ms and % ms pl = S. mutans counts and % of total streptococci in saliva and plaque; strept, strept pl = total streptococcal counts in saliva, plaque; IBadh = S. mutans adhesion, % and tot; LY7adh = A. oris adhesion, % and tot; Db, Pa etc. = quantitative acidic PRP variants from electrophoresis; PRPtot = total amounts of PRPs.

Fig. 3

P4a children had more caries from orthodontic treatment, low S. mutans-binding and basic PRB4 allelic variation. (A) Treatment with orthodontic multibrackets between 12 and 17 years of age compared to P1 children, (B) Low versus high DMBT1-mediated binding of S. mutans to individual salivas coated onto hydroxyapatite beads; (CD) Heterozygocity at PRB4 SNP 4-2 (rs7138858) and SNP 4-3 (rs1863843) coincided with increased caries in P4a and P6 children respectively. The p-values were obtained using chi2 test (frequencies) or Mann-Whitney U test (ΔDeFS).

Fig. 4

Relationship between acidic PRP phenotypes and adhesion of indigenous and cariogenic model bacteria. (A) Caries and saliva adhesion of indigenous and pathogenic bacteria in P4, P6 and P1 children. Data are from adhesion to individual saliva's and presented as mean adhesion (95% CI). (B) Pattern cognition of phenotypes P1-P10 and (C) nearly linear prediction of observed adhesion of S. gordonii SK12 (R2 = 78%, Q2 = 56%) upon PLS prediction modeling of acidic PRP allelic composition and amounts against indigenous adhesion of A.oris and S. gordonii model bacteria to individual saliva's (n = 218 children). Adhesion increases from left to right in each phenotype as the amount of acidic PRPs increases (marked by circles and brackets).