Genetic Association of MPPED2 and ACTN2 with Dental Caries

B O C Stanley; E Feingold; M Cooper; M M Vanyukov; B S Maher; R L Slayton; M C Willing; S E Reis; D W McNeil; R J Crout; R J Weyant; S M Levy; A R Vieira; M L Marazita; J R Shaffer

doi:10.1177/0022034514534688

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Genetic Association of MPPED2 and ACTN2 with Dental Caries

Journal article

Open access

Peer reviewed

Genetic Association of MPPED2 and ACTN2 with Dental Caries

B O C Stanley, E Feingold, M Cooper, M M Vanyukov, B S Maher, R L Slayton, M C Willing, S E Reis, D W McNeil, R J Crout, …

Journal of dental research, Vol.93(7), pp.626-632

07/2014

DOI: 10.1177/0022034514534688

PMCID: PMC4107549

PMID: 24810274

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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.

Metalloendopeptidases - genetics

European Continental Ancestry Group - genetics

Genome-Wide Association Study

Edar-Associated Death Domain Protein - genetics

Lipoproteins - genetics

Membrane Proteins - genetics

Humans

Middle Aged

African Americans - genetics

Child, Preschool

Male

Phosphoric Diester Hydrolases - genetics

Dental Caries - genetics

Young Adult

Actinin - genetics

Adolescent

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics

Polymorphism, Single Nucleotide - genetics

Adult

Female

Receptor, EphA7 - genetics

Child

Amelogenesis - genetics

Details

Title: Subtitle: Genetic Association of MPPED2 and ACTN2 with Dental Caries
Creators: B O C Stanley - Department of Mathematics, Vanderbilt University, Nashville, TN, USA
E Feingold - 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
M Cooper - 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
M M Vanyukov - University of Pittsburgh
B S Maher - Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, USA
R L Slayton - Department of Pediatric Dentistry, School of Dentistry, University of Washington, Seattle, WA, USA
M C Willing - Division of Genetics and Genomics, Medicine, Department of Pediatrics, School of Medicine, Washington, University at St. Louis, St. Louis, MO, USA
S E Reis - 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
D W McNeil - Dental Practice and Rural Health, West Virginia University, Morgantown, WV, USA
R J Crout - Department of Periodontics, School of Dentistry, West Virginia University, Morgantown, WV, USA
R J Weyant - Department of Dental Public Health and Information Management, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
S M Levy - 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
A R Vieira - 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
M L Marazita - University of Pittsburgh
J R Shaffer - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA jrs51@pitt.edu
Resource Type: Journal article
Publication Details: Journal of dental research, Vol.93(7), pp.626-632
Publisher: United States
DOI: 10.1177/0022034514534688
PMID: 24810274
PMCID: PMC4107549
ISSN: 0022-0345
eISSN: 1544-0591
Grant note: R01 DE014899 / NIDCR NIH HHS U01 DE018903 / NIDCR NIH HHS P50-DA005605 / NIDA NIH HHS U01-DE018903 / NIDCR NIH HHS R01-DE012101 / NIDCR NIH HHS R01-DE014899 / NIDCR NIH HHS R01 DE009551 / NIDCR NIH HHS R01 DE018914 / NIDCR NIH HHS R01 DE012101 / NIDCR NIH HHS UL1 TR000005 / NCATS NIH HHS R01-DE009551 / NIDCR NIH HHS R01-DE018914 / NIDCR NIH HHS P50 DA005605 / NIDA NIH HHS R01-DA019157 / NIDA NIH HHS R01 DA019157 / NIDA NIH HHS
Language: English
Date published: 07/2014
Academic Unit: Preventive and Community Dentistry; Epidemiology; Pediatric Dentistry
Record Identifier: 9983917679002771

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