{"id":33994,"date":"2025-07-31T03:17:13","date_gmt":"2025-07-31T03:17:13","guid":{"rendered":"https:\/\/www.newsbeep.com\/au\/33994\/"},"modified":"2025-07-31T03:17:13","modified_gmt":"2025-07-31T03:17:13","slug":"polygenic-architecture-of-dental-caries-single-nucleotide-polymorphisms-in-genetic-epidemiology","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/au\/33994\/","title":{"rendered":"Polygenic architecture of dental caries: single nucleotide polymorphisms in genetic epidemiology"},"content":{"rendered":"

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The figure illustrates the major categories of genes that may influence susceptibility to dental caries, organized by their biological functions and pathways. These groups include: (1) Enamel formation genes, which play roles in the development and mineralization of the tooth enamel and dentin; (2) Immune response genes, involved in innate and adaptive immune mechanisms that modulate the host response to cariogenic bacteria; (3) Saliva-related genes, which influence the composition, flow, and buffering capacity of saliva, impacting oral microbiota and caries risk; (4) Taste perception genes, which may affect dietary preferences and sugar intake, indirectly influencing caries development; Each group contributes to different aspects of carie<\/p>\n

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Credit: Luiz Alexandre Chisini<\/p>\n

Dental caries remains a significant global public health burden, affecting billions worldwide despite preventive measures. While behavioral and socioeconomic factors are primary drivers, individual susceptibility varies markedly among those with similar risk profiles. This review synthesizes evidence establishing a substantial genetic component in caries etiology, mediated through polygenic mechanisms and epistatic interactions across key biological pathways.<\/p>\n

Genetic Pathways and Key Findings<\/p>\n

1. Tooth Mineralization Genes:<\/p>\n

Key Genes:\u00a0AMBN,\u00a0AMELX,\u00a0ENAM,\u00a0MMPs\u00a0(e.g.,\u00a0MMP2,\u00a0MMP20),\u00a0KLK4,\u00a0TFIP11,\u00a0BMP7,\u00a0*DLX3\/DLX4*.<\/p>\n

Mechanism:\u00a0Variants alter enamel\/dentin structure and mineralization, increasing susceptibility to acid demineralization. Epistatic interactions (e.g.,\u00a0*TUFT1-MMP2-TFIP11*,\u00a0*MMP2-BMP7*) significantly influence lifelong caries trajectories, often undetected by single-SNP analyses. Meta-analyses confirm associations (e.g.,\u00a0AMELX\u00a0OR=1.78,\u00a0TFIP11\u00a0OR=1.64).<\/p>\n

2. Taste Perception Genes:<\/p>\n

Key Genes:\u00a0TAS2R38\u00a0(bitter),\u00a0TAS1R2,\u00a0TAS1R3\u00a0(sweet).<\/p>\n

Mechanism:\u00a0SNPs (e.g.,\u00a0TAS2R38\u00a0rs713598) alter taste sensitivity, influencing sugar preference and intake. The CG genotype of rs713598 is protective (OR=0.35).\u00a0TAS1R3\u00a0rs307355 shows dose-dependent caries risk across life stages, with epistasis between\u00a0*TAS1R2\/TAS1R3*. GWAS consistently implicate\u00a0TAS2R\u00a0genes.<\/p>\n

3. Salivary Genes:<\/p>\n

Key Genes:\u00a0CA6,\u00a0AQP5,\u00a0MUC5B.<\/p>\n

Mechanism:\u00a0Variants impact saliva flow, buffering capacity (CA6), and antimicrobial properties (MUC5B).\u00a0CA6\u00a0rs17032907-TT increases risk 3.23-fold;\u00a0AQP5\u00a0variants are protective (OR=0.75). Reduced\u00a0MUC5B\u00a0facilitates\u00a0S. mutans\u00a0adhesion. GWAS link\u00a0CA12\u00a0(salivary buffering) to caries.<\/p>\n

4. Immune Response Genes:<\/p>\n

Key Genes:\u00a0MBL2,\u00a0LTF,\u00a0DEFB1.<\/p>\n

Mechanism:\u00a0Polymorphisms impair innate immunity (e.g.,\u00a0MBL2\u00a0rs11003125-CG\/GG), reducing antimicrobial action against cariogenic biofilms. Pooled\u00a0MBL2\u00a0SNPs increase risk (homozygote OR=2.12; heterozygote OR=2.22).<\/p>\n

Genome-Wide vs. Candidate Gene Studies<\/p>\n

GWAS\u00a0identified novel loci (AJAP1,\u00a0ADAMTS3,\u00a0ISL1,\u00a0BCOR) beyond traditional pathways, implicating odontogenesis, neural function, and immune regulation. Taste (TAS2R) and mineralization (*DLX3\/DLX4*) pathways were validated.<\/p>\n

Limited Overlap:\u00a0Discrepancies arise from GWAS’ stringent significance thresholds, phenotypic heterogeneity (DMFT vs. ICDAS), population stratification, and inadequate power\/corrections in candidate studies.<\/p>\n

Critical Methodological Challenges<\/p>\n

Population Stratification:\u00a0Inadequate control for genetic ancestry confounds associations. Self-reported race is insufficient; genomic control (e.g., PCA) is essential.<\/p>\n

Hardy-Weinberg Equilibrium (HWE):\u00a0Deviations may indicate genotyping errors or bias; pre-analysis HWE checks are crucial.<\/p>\n

Linkage Disequilibrium (LD):\u00a0Failure to account for LD biases epistasis and association results.<\/p>\n

Multiple Testing:\u00a0Bonferroni corrections are fundamental but rarely applied, inflating false positives (e.g., only 17% of candidate studies corrected adequately).<\/p>\n

Epistasis:\u00a0Single-SNP analyses overlook complex interactions; advanced models (e.g., polygenic risk scores) are needed.<\/p>\n

Conclusions and Future Directions<\/p>\n

Dental caries is a polygenic trait shaped by interactions across enamel integrity, taste preference, salivary function, and immunity. Future studies must:<\/p>\n

Employ larger, diverse cohorts with standardized phenotyping.<\/p>\n

Integrate epistasis, gene-environment interactions, and polygenic risk scores.<\/p>\n

Rigorously address ancestry, LD, HWE, and multiple testing.<\/p>\n

Prioritize translational applications, such as genetic panels for high-risk identification and personalized prevention.<\/p>\n

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Full text<\/p>\n

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The study was recently published in the\u00a0Gene Expression<\/a>.<\/p>\n

Gene Expression<\/a>\u00a0(GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc. \u00a0\u00a0<\/p>\n

GE publishes peer-reviewed and high-quality original articles, reviews, editorials, commentaries, and opinions on its primary research topics including cell biology, molecular biology, genes, and genetics, especially on the cellular and molecular mechanisms of human diseases.\u00a0<\/p>\n

GE has been indexed in Medline (1991-2021), Scopus, Biological Abstracts, Biosis Previews, ProQuest, etc.<\/p>\n

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Article Title<\/p>\n

Polygenic Architecture of Dental Caries: Single Nucleotide Polymorphisms in Genetic Epidemiology<\/p>\n

Article Publication Date<\/p>\n

1-Jul-2025<\/p>\n

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.<\/p>\n