Association of genetic variants in enamel-formation genes with dental caries: A meta- and gene-cluster analysis

Previous studies have reported the association between multiple genetic variants in the enamelformation 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 the enamel-formation genes and the risk of dental caries. We 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 was associated with dental caries, and multiple genetic variants in the enamel-formation genes jointly contributed to the risk of dental caries, supporting the role of genetic variants in the enamelformation genes in the etiology of dental caries. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.