Dataset Information

Genetic Association of MPPED2 and ACTN2 with Dental Caries.

ABSTRACT: The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.

SUBMITTER: Stanley BO

PROVIDER: S-EPMC4107549 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Genetic Association of MPPED2 and ACTN2 with Dental Caries.

Stanley B O C BO Feingold E E Cooper M M Vanyukov M M MM Maher B S BS Slayton R L RL Willing M C MC Reis S E SE McNeil D W DW Crout R J RJ Weyant R J RJ Levy S M SM Vieira A R AR Marazita M L ML Shaffer J R JR

Journal of dental research 20140508 7

The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were com ...[more]

PMID: 24810274

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Project description:AimDental enamel, the most rigid biological tissue of the tooth known to mankind, is the most integral and fundamental part of the tooth. Enamel matrixes compile 5% of Enamelin peptides and at the time of tooth development, they are considered to effect the formation and elongation of enamel crystallites. ENAM plays critical role in enamel formation. Any changes in ENAM may affect the thickness of enamel and may lead to dental caries. The present study is aimed to evaluate the association of ENAM gene polymorphisms and susceptibility of dental caries development risk.Material and methodsThe present study was carried out on 168 South Indian children, children's with dental caries were included in study. Written consent was taken from their parents/guardians. Additionally 193 healthy individuals were enrolled as controls. Sampling was done after dental examination of the individuals. Three ENAM gene single nucleotide polymorphisms (SNPs) were rs7671281, rs3796704 and rs12640848 was genotyped to check their role in susceptibility of dental caries development risk.ResultsOut of three SNPs rs7671281 showed statistically significant risk association with dental caries susceptibility in this ethnic population at heterozygous allele CT (OR: 1.939, p = .01865) and with minor allele T (OR: 1.451, p = .001292). SNP rs3796704 showed significant protective association with dental caries in Indian population at heterozygous allele GA (OR: 0.409, p = .0192) and with minor allele A (OR: 0.645, p = .00875). SNP rs12640848 showed significant protective association with dental caries in Indian population at heterozygous allele AG (OR: 3.041, p = .00642) and with minor allele G (OR: 1.478, p = .02184). Preliminary insilico analysis also showed that rs7671281 (Ile648Thr) amino acid change will cause the structural and functional changes in ENAM protein.ConclusionsIn the present study significant association was observed between ENAM gene SNP rs7671281 and dental caries susceptibility in South Indian children. These results suggested that ENAM gene variants may contribute to dental caries in children.

Project description:BackgroundThe pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results.MethodsA systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants in LTF were available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by using random-effects models to assess the association of genetic variants in LTF with the risk of dental caries. We also performed a gene-based analysis to explore the joint association of multiple genetic variants in LTF with the risk of dental caries.ResultsOur systematic literature search identified six relevant papers for analysis. We found no significant association between rs1126478 and the risk of dental caries when meta-analysing the genotype distribution between subjects with dental caries and those without dental caries (additive model: OR = 1.41; 95% CI = 0.98-2.02; P = 0.065). However, further analysis indicated that rs1126478 was associated with dental risk in subjects who had moderate or severe dental caries compared to those without dental caries (P < 0.0001). The gene-based analysis indicated that multiple genetic variants in LTF were jointly associated with the risk of dental caries (P = 0.002).ConclusionsThe present meta-analysis revealed some evidence of the association between rs1126478 and dental caries and that multiple genetic variants in LTF are jointly associated with the risk of dental caries. Our findings need to be validated by larger studies that adjust for important confounding factors for the risk of dental caries.

Dataset Information

Genetic Association of MPPED2 and ACTN2 with Dental Caries.

Publications

Genetic Association of MPPED2 and ACTN2 with Dental Caries.

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