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.
Gene Cluster Analysis Method Identifies Horizontally Transferred Genes with High Reliability and Indicates that They Provide the Main Mechanism of Operon Gain in 8 Species of γ-Proteobacteria