Genetic Variants and Dental Caries Susceptibility: An Umbrella Review and Multilevel Meta-Analysis.

Objective: This umbrella review aimed to evaluate the strength and consistency of evidence linking genetic variants to dental caries susceptibility. Methods: An umbrella review was conducted, following PRISMA 2020 guidelines. A comprehensive literature search was performed across six databases. Eligibility criteria included systematic reviews and meta-analyses of human subjects. Study selection, data extraction, and methodological quality assessment were performed systematically, with quality evaluated using the AMSTAR-2 tool. Multilevel meta-analyses were conducted to assess variant-specific and grouped genetic effects. Results: The search identified 29 eligible systematic reviews and meta-analyses for inclusion. The multilevel meta-analysis showed statistically significant associations for polymorphisms in TAS2R38 rs713598 (OR = 0.26, 95% CI: 0.09-0.73) and VDR Cdx-2 rs11568820 (OR = 0.66, 95% CI: 0.46-0.95), both indicating lower odds of dental caries, while MBL2 rs1800450 was associated with increased odds (OR = 1.48, 95% CI: 1.03-2.14). However, pooled effects across the main gene categories, including tooth development and mineralization, salivary composition and function, immune and inflammatory response, taste perception, and signaling, were not statistically significant. Findings were heterogeneous across studies. Conclusions: Current evidence on the association between genetic variants and dental caries susceptibility remains limited and inconsistent, providing insufficient support for the use of genetic markers in risk assessment or personalized prevention. The significant single-nucleotide polymorphism (SNP) associations identified in this review are hypothesis-generating and require validation in larger and more diverse populations using standardized caries definitions and gene-environment approaches.