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Previous studies have reported the association between multiple genetic variants in enamel formation-related genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in enamel- formation-related genes and the risk of dental caries. Our systematic literature search identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR=1.40, 95% CI: 1.02-1.93, P=0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR=1.15, 95% CI: 0.88-1.52, P=0.310), rs1784418 in MMP20 (OR=1.07, 95% CI: 0.76-1.49, P=0.702) and rs3796704 in ENAM (OR=1.06, 95% CI: 0.96-1.17, P=0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P<10-5), so did genetic variants in MMP13 (3 variants; P=0.004), MMP2 (3 variants; P<10-5), MMP20 (2 variants; P<10-5) and MMP3 (2 variants; P<10-5). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P<10-5). The present meta-analysis revealed that genetic variant rs17878486 in AMELX were associated with dental caries, and multiple genetic variants in enamel-formation-related genes jointly contribute to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.

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