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. 2019 May 30;11(2):19.
doi: 10.1038/s41368-019-0051-4.

Human Genes Influence the Interaction Between Streptococcus Mutans and Host Caries Susceptibility: A Genome-Wide Association Study in Children With Primary Dentition

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Free PMC article

Human Genes Influence the Interaction Between Streptococcus Mutans and Host Caries Susceptibility: A Genome-Wide Association Study in Children With Primary Dentition

Ying Meng et al. Int J Oral Sci. .
Free PMC article

Abstract

Streptococcus mutans is a well-known cause of dental caries, due to its acidogenicity, aciduricity, and ability to synthesize exopolysaccharides in dental plaques. Intriguingly, not all children who carry S. mutans manifest caries, even with similar characteristics in oral hygiene, diet, and other environmental factors. This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries; however, the association between host genetics, S. mutans, and dental caries remains unclear. Therefore, this study examined the influence of host gene-by-S. mutans interaction on dental caries. Genome-wide association analyses were conducted in 709 US children (<13 years old), using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS). A generalized estimating equation was used to examine the gene-by-S. mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries). Sequentially, the COHRA and GEIRS data were used to identify potential interactions and replicate the findings. Three loci at the genes interleukin 32 (IL32), galactokinase 2 (GALK2), and CUGBP, Elav-like family member 4 (CELF4) were linked to S. mutans carriage, and there was a severity of caries at a suggestive significance level among COHRA children (P < 9 × 10-5), and at a nominal significance level among GEIRS children (P = 0.047-0.001). The genetic risk score that combined the three loci also significantly interacted with S. mutans (P < 0.000 1). Functional analyses indicated that the identified genes are involved in the host immune response, galactose carbohydrate metabolism, and food-rewarding system, which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The relationship between dental caries and S. mutans carriage. *Indicates P< 0.05. S. mutans+ means positive for S. mutans carriage. S. mutans– means negative for S. mutans carriage
Fig. 2
Fig. 2
Genome-wide SNP-by-S. mutans interaction analysis results. a Manhattan plot for dmft. b Manhattan plot for dmftw. In both subfigures, the red line represents the genome-wide significant level; the green line represents the suggestive significance level; the red dots represent the SNPs identified in the study
Fig. 3
Fig. 3
Marginal effect of SNP-by-S. mutans interaction on caries (dmft). The marginal effect was estimated using the GEE negative binomial models adjusting for age, gender, race, and five eigenvectors. *P < 0.05. a Marginal effect of rs4786370-by-S. mutans interaction on dmft. b Marginal effect of rs11635005-by-S. mutans interaction on dmft. c Marginal effect of rs1539849-by-S. mutans interaction on dmft d Marginal effect of the GRS on dmft
Fig. 4
Fig. 4
The impact of effective alleles on gene expression. The labels were organized as SNP_effective allele_reference allele_tissue. The slope values were obtained from SNP-gene association tests conducted by GTEx. A positive slope value indicates that the effect allele is associated with increased gene expression. *P < 0.05

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