Salivary protein polymorphisms and risk of dental caries: a systematic review

LIPS, Andrea; ANTUNES, Leonardo Santos; ANTUNES, Lívia Azeredo; PINTOR, Andrea Vaz Braga; SANTOS, Diana Amado Baptista dos; BACHINSKI, Rober; KÜCHLER, Erika Calvano; ALVES, Gutemberg Gomes

doi:10.1590/1807-3107BOR-2017.vol31.0041

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Systematic Review • Braz. oral. res. 31 • 2017 • https://doi.org/10.1590/1807-3107BOR-2017.vol31.0041 linkcopy

Salivary protein polymorphisms and risk of dental caries: a systematic review

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Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: “dental caries susceptibility,” “dental caries,” “polymorphism, genetics,” “saliva,” “proteins,” and “peptides.” Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.

Dental Caries; Polymorphism, Genetic; Saliva; Proteins

Criteria evaluated	Articles

	Tao et al., 2005	Zakhary et al., 2007	Azevedo et al., 2010	Ozturk et al., 2010	Peres et al., 2010	Bancher et al., 2011	Pol et al., 2011	Yarat et al., 2011	Buczkowska-Radlinska et al., 2012	Fine te al., 2013	Shaffer et al., 2013	Volckva et al., 2014	Abbasoğlu et al., 2015	Doetzer et al., 2015	Li et al., 2015	Yildiz et al., 2016
Control group	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Hardy–Weinberg equilibrium	0	1	0	1	0	0	0	0	0	0	1	1	1	1	1	0
Case group	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Primer	0	0	1	0	1	1	0	1	1	1	0	1	0	1	1	1
Reproducibility	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Blinding	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Power calculation	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Statistics	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Corrected statistics	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Independent replication	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Compilation of reported associations and outcomes	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Score	8	10	9	9	9	9	8	9	9	9	9	10	10	10	10	9

Authors	Population	n	Age range (years)	Caries index (low ; high)	Protein	Gene	Location	Genetic variation	Function	Molecular biology technique	Results
Tao et al., 2005	USA Hispanic; Caucasian	149 children	11-15	DMFT/dmft (0 ; ≥ 1)	Human beta defensin 1 (HBD1)	DEFB1	Chromosome 8 (23.1)	rs11362, rs1800972	Antimicrobial	PCR- TaqMan assay	No significant association
Zakhary et al., 2007	USA African-descent, Caucasian and Mixed	208 children; 50 adults	\	DMFT/dmft (0 ; ≥ 4)	Acidic Proline-rich Protein Db	PRH1	Chromosome 12 (13.2)	Db absent, Db present	bacterial attached to biofilm	PCR-RFLP	No significant association
Azevedo et al., 2010	Brazil Caucasian	110 children	12	DMFT/dmft (0 ; ≥ 1)	Lactotransferrin	PRH1	Chromosome 3 (21)	Second Exon (AA, AG, GG)	Antibacterial	PCR-SSCP	Association between LTF A/G and low dental caries experience
Ozturk et al.	USA Caucasian, African-American	296 adults	17-84	DMFT/dmft [(< 14; > 14) up 30 years; (< 9; > 9) under 30 years]	HBD1	HBD1	Chromosome 8 (23.1)	rs11362, rs1800972	Antimicrobial	RT-PCR	Association of rs179946 with low DMFT score, and rs11362 with high DMFT
Peres et al., 2010	Brazil Caucasian, Black	245 children	7-9	DMFT/dmft (= 0 ; ≥ 1)	Carbonic anhydrase VI	CA VI	Chromosome 1(36.2)	rs2274327, rs2274328rs2274333	pH regulation	PCR-RFLP	Association between rs2274327 and buffer capacity
Brancher et al., 2011	Brazil Caucasian	50 chldren	12	DMFT/dmft (= 0 , ≥ 4)	Lactotransferrin	LTF	Chromosome 3 (21)	Biomarkers in promoter region	Antibacterial	PCR-SSCP	No significant association
Pol J, 2011	Poland Caucasian	158 adults	20-21	DMFT (≤ 7 ; ≥ 15)	Mucin	MUC7	Chromosome 4 (13.21)	MUC7 5/5, MUC 7 5/6., MUC7 6/6	Formation of dental pellicle	PCR-RFLP	Association between MUC7 6/6 genotype and high dental caries experience
Yarat et al., 2011	Turkey	44 adults	18-26	DMFT (< 6 ; ≥ 6)	Carbonic anhydrase VI	CA VI	Chromosome 1(36.2)	Rs2274327, Rs227428	pH regulation	DNA sequencing	No association between biomarker and low caries experience
Yarat et al., 2011	Turkey	44 adults	18-26	DMFT (< 6 ; ≥ 6)	Carbonic anhydrase VI	CA VI	Chromosome 1(36.2)	Rs2274327, Rs227428	pH regulation	DNA sequencing	High experience group absent in the study
Buczkowska-Radlinska et al., 2012	Poland Caucasian	158 adults	20-21	DMFT (≤ 7 ; ≥ 15)	Mucin	MUC7	Chromosome 4 (13.21)	MUC7 5/5, MUC 7 5/6., MUC7 6/6	Formation of dental pellicle	PCR-RFLP	No significant association
Fine et al., 2013	USA	30 adults	29-38	DMFT	Lactotransferrin	LTF	Chromosome 3 (21)	KK, KR, RR	Antibacterial	PCR-RFLP	LTF/K variance can influence caries susceptibility
Shaffer et al., 2013	USA Caucasian	920 adults	18-75	DMFT and DMFTS	LYZL2	LYZL2	Chromosome 10 (11.23)	rs399593	Bacteriolytic factor	DNA sequencing	Association with mandibular anterior surfaces
Volckova et al., 2014	Czeh, Caucasian	637 children	2-5	DMFT/dmft (= 0; ≥ 1)	Lactotransferrin	LTF	Chromosome 3 (21)	rs1126478	Antibacterial	PCR-RFLP	No significant association
Abbasoğlu et al., 2015	Turkish	259 children	2-5	DMFT/dmft (0 ; ≥ 1)	Lactotransferrin, HBD1	LTF, defb1	Chromosome 3 (21), Chromosome 8 (23.1)	rs2269436, rs743658, rs4547741, rs17078878, rs4547741	Antibacterial, Antimicrobial	RT-PCR	CT in LTF (rs4547741) protective for caries
Doetzer et al., 2015	Brazil, Caucasian	677 children	12	DMFT/dmft (0 ; ≥ 1)	Lactotransferrin	LTF	Chromosome 3 (21)	rs6441989, rs2073495, rs11716497	Antimicrobial	PCR-SSCP	Allele A for rs6441989 protected for caries
Li et al., 2015	Chinese	355 adults	mean age = 48	DMFT (≤ 2; > 3)	Carbonic anhydrase VI	CA VI	Chromosome 1(36.2)	Several SNPs in intron regions	pH regulation	DNA sequencing	rs17032907 and haplotype (ACA) associated with caries susceptibility
Yildiz et al., 2016	Turkish	15 adults	not provided	DMFT (≤ 5; ≥ 14)	Carbonic anhydrase VI	CA VI	Chromosome 1(36.2)	rs2274327	Antibacterial	PCR-RFLP	rs11362 positively associated with caries experience
					HBD1	DEFB1	Chromosome 8 (23.1)	rs11362	Antimicrobial

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[TFN1] For the quantification of criteria: “1” means present and “0” means absent.