Table 1.

Candidate genes studied for erosion in humans.

Genes	Function	Results and conclusion	Reference
Enamelin (ENAM) rs12640848	Enamel formation gene. Mineralization and structural organization of the enamel [16].	Analysis based on differences in allele frequency showed a statistically significant association with dental erosion and the ENAM rs12640848 marker. The frequency of the G allele of ENAM rs12640848 was significantly higher in the erosion group than in the nonerosion group.	Sovik et al. [31]
Amelogenin (AMELX) rs946252	Enamel formation gene. Mineralization during tooth enamel development [16].	When erosion severity was considered, statistically significant differences in allele frequency were observed for the AMELX rs946252 marker, with the C allele suggesting a protective role. An over-representation of the TT genotype of the AMELX marker was seen in cases with severe erosion. AMELX was also associated with severe erosion when the recessive model was considered; the TT genotype was significantly more frequent in the affected group than in the unaffected group. Association with severe dental erosion and the AMELX rs946252	Sovik et al. [31]
		When analyzing the terciles, significant associations were found between enamel loss and the AMELX rs946252. When comparing allele and genotype distributions between individuals more and less susceptible to enamel loss, no statistically significant differences were found.	Uhlen et al. [28]
Ameloblastin (AMBN) rs4694075	Enamel formation gene. Involved in enamel matrix formation and mineralization [16].	No evidence of association	Sovik et al. [31]
Tuftelin 1 (TUFT1) rs7526319	Enamel formation gene. Expressed in the developing and mineralized tooth [16].	No evidence of association	Sovik et al. [31]
Tuftelin 1 (TUFT1) rs4970957	Enamel formation gene. Expressed in the developing and mineralized tooth [16].	When analyzing the terciles, significant associations were found between enamel loss and the TUFT1 rs4970957. When comparing allele and genotype distributions between individuals more and less susceptible to enamel loss, no statistically significant differences were found.	Uhlen et al. [28]
Tuftelin-interacting protein 11 (TFIP11) rs5997096	Enamel formation gene. Thought to interact with tuftelin and can play a role in spliceosome disassembly in Cajal bodies [32].	No evidence of association	Sovik et al. [31]
Tuftelin-interacting protein 11 (TFIP11) rs134136 and rs5997096	Enamel formation gene. Thought to interact with tuftelin and can play a role in spliceosome disassembly in Cajal bodies [32].	When analyzing the terciles, significant associations were found between enamel loss and the both TFIP11 SNPs rs134136 and rs5997096. When comparing allele and genotype distributions between individuals more and less susceptible to enamel loss, no statistically significant differences were found.	Uhlen et al. [28]
SNP rs11681214 (located between peroxidasin (PXDN) and myelin transcription factor 1 like (MYT1L)	PXDN is involved in extracellular matrix formation and encodes a proteolytic enzyme, peroxidase, which is the main salivary antioxidant and found in the organic matrix of the enamel pellicle [33]	Statistically significant association between dental erosion and PXDN and MYT1L	Alaraudanjoki et al. [34]
(IRX1, IRX4) rs493321	Clustered near genes already proposed to be involved in embryogenesis or tooth development	Suggestively significant association between tooth wear and IRX1, IRX4 rs493321	Alaraudanjoki et al. [34]
Chromosome 8 open reading frame 86, fibroblast growth factor receptor 1 (C9orf86, FGFR1) rs11993596, rs112007639, rs12546327, and rs2461333	C8orf86's function is unknown. FGFR1 has been proposed to be the major receptor in the regulation mechanisms of fibroblast growth factor signals in human tooth development [35] and is involved in molar-incisorl hypoplasia [36]. FGFR1 also participates in the regulation of differentiation and secretory functions of odontoblasts and ameloblasts [37], and its role has been found to be critical in the formation of proper enamel [38].	Significant association between dental wear and C9orf86, FGFR1 rs11993596, rs112007639, rs12546327, and rs2461333 among males	Alaraudanjoki et al. [34]
(PRMT8) rs768398	Clustered near genes already proposed to be involved in embryogenesis or tooth development	Suggestively significant association between dental wear and PRMT8 rs768398	Alaraudanjoki et al. [34]
Cadherin 4 (CDH4) rs2426986, rs16984837, and rs6101273	The encoded protein (R-cadherin) is a calcium-dependent cell-cell adhesion glycoprotein, which is highly expressed in oral mucosa and also linked to both Wnt and FGF signaling [39]. Recently, it has been shown that CDH4 also promotes the expression of E-cadherin [40], which plays a crucial role in enamel development [41].	Statistically significant association between dental wear and CDH4 rs2426986, rs16984837, and rs6101273 among males	Alaraudanjoki et al. [34]
γ-protocadherin (PCDHG@) chr5: 141405828)	PCDHG@ is believed to modulate regulatory pathways critical for development, such as Wnt signaling (63), which is also critical at all stages of tooth development [34]	Evidence of a significant association in the GWAS on men, and the associations were also suggestively significant in the whole-sample GWAS	Alaraudanjoki et al. [34]
Fibroblast growth factor 1 (FGF1) and sprouty RTK signaling antagonist 4 (SPRY4) rs66756037	FGF1 and SPRY4 are involved in tooth development [42, 43]	The results demonstrate that there are loci in the genome that are directly associated with erosive wear. There is a difference between women and men in the genes associated with erosive tooth wear.	Alaraudanjoki et al. [34]
Stearoyl-CoA desaturase 5 (SCD5) chr4: 82684912	SCD5 has a role in activating the noncanonical Wnt pathway [44] as well as impairing cathepsin B secretion [45]. Cathepsin B is expressed during the maturation stage of the enamel [46] and also apparently has a role in dentine degradation [47].	Statistically significant association between dental wear and SCD5 chr4: 82684912 among females. In addition, 19 suggestive SNPs were identified near chr4: 82684912. Interestingly, this polymorphism is located in the chromosomal region 4q21 in which the genetic variation seems to impact dental caries experience and near locus 4q22, which showed the strongest suggestive association signal in the dental caries GWAS and harbors several tooth-related genes	Alaraudanjoki et al. [34]
Coagulation factor II thrombin receptor (F2R), F2R-like trypsin receptor 1 (F2RL1) chr5: 76795786	F2R, encoding protease-activated receptor 1 (PAR1), has recently been suggested to be highly expressed in secretory stage ameloblasts [48] and thus may have a critical role in the formation of proper enamel. This locus was also suggestive in the whole-sample GWAS and has been studied further in a fine-mapping study concerning dental caries [49].	Statistically significant association between dental wear and F2R, F2RL1 chr5: 76795786 among females	Alaraudanjoki et al. [34]
Msh homeobox 1 (MSX1) chr4	MSX1 is important for the tooth development [50]	A cluster of suggestive SNPs found near this gene when using the extreme opposite approach	Alaraudanjoki et al. [34]
Aquaporin 2 (AQP2) chr12: rs2878771	Potential involvement in immune response and salivary contribution [51]	Association found for genotypic (p=0.02) and dominant (p=0.03) models using logistic regression analysis, with the assumption that the dental erosive wear is a gene-environment complex model	Tulek et al. [2020] [52]
Aquaporin 5 (AQP5) chr12: rs3739306	Potential involvement in immune response and salivary contribution [53]	Association found for allelic model (p=0.02) using logistic regression analysis, with the assumption that the dental erosive wear is a gene-environment complex model	Tulek et al. [52]