Dental caries is caused by the acidic environment that results from carbohydrate metabolism when sugars are introduced to the oral microbiome.
14-16 Enamel and dentin structure, immune response, salivary content and volume, and oral microbiota contribute to the multifactorial and complex etiology of dental caries,
16-18 but the extent to which susceptibility to caries is under genetic control, and which genes may be involved, is the subject of some debate.
Discovery of a direct role of individual gene variants in the etiology of caries has met with inconsistent results. Twin studies have suggested partial genetic control, from as low as around 20%
19, 20 to as high as 85%.
20-22 The wide range of heritability may partially be due to etiological variation of caries experience, including population or race-level genetic or environmental differences. Despite potential genetic control of caries susceptibility, early childhood caries experience may be strongly influenced by maternal health or obesity,
23 and “[l]iving in a rural area, low socioeconomic status, less frequent tooth cleaning and sugar containing soft drinks [are] associated with a higher prevalence of dental caries.”
24 Genes consistently associated with caries experience in recent studies are listed in Table 1, below.
Table 1. Genes believed to be involved in caries experience
Gene |
Role |
Associated Disease |
Ameloblastin (AMBN)
|
Enamel matrix
|
Caries,25 dental fluorosis26
|
Amelogenin (AMELX)
|
Tooth mineralization
|
Amelogenesis imperfecta4, caries27-29
Molar incisor hypomineralization30, 31 |
Aquaporin 5 (AQP5)
|
Saliva production
|
Caries32 (possibly protective)21
|
Carbonic Anhydrase VI (CA6)
|
Saliva pH regulation
|
Caries9, 33
|
Enamelin (ENAM)
|
Enamel matrix
|
Amelogenesis imperfecta4, molar incisor hypomineralization31, caries34-38
|
Estrogen related receptor beta (ESRRB)
|
Enamel hardness
|
Caries,11, 32, 39 hearing impairment39
|
Kallikrein 4 (KLK4)
|
Enamel matrix strengthening
|
Hypomaturation amelogenesis imperfecta40, 41
|
Matrix metalloproteinase 16 (MMP16)
|
Degradation of extracellular proteins
|
Caries42
|
Matrix metalloproteinase 20 (MMP20)
|
Early stages of tooth development
|
Caries43, 44 (possibly protective in some populations45)
|
Mucin 5 (MUC5B)
|
Inhibits biofilm formation
|
Caries susceptibility46
|
Polycystin-2 (PKD2)
|
Transient receptor potential channel
|
Polycystic kidney disease; caries47, 48
|
Tuftelin 1 (TUFT1)
|
Enamel matrix
|
Caries49, 50
|
Tuftelin-interacting protein 11 (TFIP11)
|
Enamel matrix
|
Caries49
|
Genetic Control of the Plaque Microbiome
Twin studies indicate that the plaque microbiome is largely hereditary and under significant genetic control in early life,
14, 51 or in emerging (primary and secondary) dentitions,
14 but environmental exposures throughout life increasingly affect the taxa present.
14, 15, 51 Acidogenic
Streptococci species are the most abundant pathogens in the oral environment, but a 2017 study
51 of 485 dizygotic and monozygotic twins found that caries experience was not associated with heritable bacteria, and argued that proliferation of cariogenic bacteria such as
Streptococci spp. is primarily a result of environmental exposure, that is, the introduction of carbohydrate-rich foods.
51 Genetic control of the oral environment is likely responsible for healthy or non-cariogenic bacteria that make up plaque during development of the dentition, including the highly-heritable
Prevotella pallens,
Veillonella spp., Pasteurellaceae, and
Croynebacterium durum, as well as potentially heritable
Leptotrichia and
Abiotophia.
51 Predominant cariogenic taxa are
Streptococcus mutans,
S. sobrinus, and
Lactobacillus spp;
29, 52 and abundance of
Corynebacterium matruchotii has been found to be correlated with high caries activity.
53 Recent studies have suggested that
Scardovia wiggsiae may also be associated with caries,
54, 55 particularly early childhood caries.
54, 56 S. mutans is largely regarded to be the most cariogenic bacterial species.
57
Archaeological studies of ancient dental plaque show that plaque microflora had become less diverse and more dominated by cariogenic
Streptococci (particularly
S. mutans) following the transition to agriculture around 10,000 years ago and again, more drastically and permanently, after the Industrial Revolution;
58, 59 both periods were marked by a shift towards carbohydrate-rich foods.
58 These studies suggest that the genetically controlled oral environment is gradually undermined by continual exposure to the modern diet.
14, 51, 58