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

Genetic Association of MPPED2 and ACTN2 with Dental Caries

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

Authors

B O C Stanley¹, E Feingold², M Cooper³, M M Vanyukov⁴, B S Maher⁵, R L Slayton⁶, M C Willing⁷, S E Reis⁸, D W McNeil⁹, R J Crout¹⁰, R J Weyant¹¹, S M Levy¹², A R Vieira³, M L Marazita¹³, J R Shaffer¹⁴

Affiliations

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.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics
Actinin / genetics*
Adolescent
Adult
Amelogenesis / genetics
Black or African American / genetics
Child
Child, Preschool
Dental Caries / genetics*
Edar-Associated Death Domain Protein / genetics
Female
Genome-Wide Association Study
Humans
Lipoproteins / genetics
Male
Membrane Proteins / genetics
Metalloendopeptidases / genetics
Middle Aged
Phosphoric Diester Hydrolases / genetics*
Polymorphism, Single Nucleotide / genetics
Receptor, EphA7 / genetics
White People / genetics
Young Adult

Substances

ACTN2 protein, human
Edar-Associated Death Domain Protein
Lipoproteins
Membrane Proteins
Actinin
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
MTR protein, human
Receptor, EphA7
MPPED2 protein, human
Phosphoric Diester Hydrolases
Metalloendopeptidases
ZMPSTE24 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding