title: 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.
authors.affiliation: Department of Mathematics, Vanderbilt University, Nashville, TN, USA.
authors.forename: B O C
authors.initials: BO
authors.lastname: Stanley
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Feingold
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Cooper
authors.affiliation: 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.
authors.forename: M M
authors.initials: MM
authors.lastname: Vanyukov
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Maher
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, University of Washington, Seattle, WA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Slayton
authors.affiliation: Division of Genetics and Genomics, Medicine, Department of Pediatrics, School of Medicine, Washington, University at St. Louis, St. Louis, MO, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Willing
authors.affiliation: 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.
authors.forename: S E
authors.initials: SE
authors.lastname: Reis
authors.affiliation: Dental Practice and Rural Health, West Virginia University, Morgantown, WV, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: McNeil
authors.affiliation: Department of Periodontics, School of Dentistry, West Virginia University, Morgantown, WV, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Crout
authors.affiliation: Department of Dental Public Health and Information Management, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Weyant
authors.affiliation: 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.
authors.forename: S M
authors.initials: SM
authors.lastname: Levy
authors.affiliation: 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.
authors.forename: A R
authors.initials: AR
authors.lastname: Vieira
authors.affiliation: 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.
authors.forename: M L
authors.initials: ML
authors.lastname: Marazita
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA jrs51@pitt.edu.
authors.forename: J R
authors.initials: JR
authors.lastname: Shaffer
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000185:Actinin / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000566:Amelogenesis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003731:Dental Caries / Q000235:genetics*; D053362:Edar-Associated Death Domain Protein / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D036141:Receptor, EphA7 / Q000235:genetics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C401401:ACTN2 protein, human; D053362:Edar-Associated Death Domain Protein; D008074:Lipoproteins; D008565:Membrane Proteins; D000185:Actinin; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; D036141:Receptor, EphA7; C561977:MPPED2 protein, human; D010727:Phosphoric Diester Hydrolases; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human
keywords: EDARADD; EPHA7; LPO; MTR; ZMPSTE24; single nucleotide polymorphism