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J Dent Res. 2014 Jul;93(7):626-32. doi: 10.1177/0022034514534688. Epub 2014 May 8.

Genetic Association of MPPED2 and ACTN2 with Dental Caries.

Author information

1
Department of Mathematics, Vanderbilt University, Nashville, TN, USA.
2
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
3
Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
4
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
5
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, USA.
6
Department of Pediatric Dentistry, School of Dentistry, University of Washington, Seattle, WA, USA.
7
Division of Genetics and Genomics, Medicine, Department of Pediatrics, School of Medicine, Washington, University at St. Louis, St. Louis, MO, USA.
8
Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
9
Dental Practice and Rural Health, West Virginia University, Morgantown, WV, USA.
10
Department of Periodontics, School of Dentistry, West Virginia University, Morgantown, WV, USA.
11
Department of Dental Public Health and Information Management, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
12
Department of Preventive and Community Dentistry, University of Iowa College of Dentistry, Iowa City, IA, USA Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
13
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
14
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA jrs51@pitt.edu.

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.

KEYWORDS:

EDARADD; EPHA7; LPO; MTR; ZMPSTE24; single nucleotide polymorphism

PMID:
24810274
PMCID:
PMC4107549
DOI:
10.1177/0022034514534688
[Indexed for MEDLINE]
Free PMC Article

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