title: Genetic Association ofMMP10,MMP14, andMMP16with Dental Caries.
abstract: Matrix metalloproteinases (MMPs), which degrade extracellular proteins as part of a variety of physiological processes, and their inhibitors have been implicated in the dental caries process. Here we investigated 28 genetic variants spanning theMMP10,MMP14, andMMP16genes to detect association with dental caries experience in 13 age- and race-stratified (n= 3,587) samples from 6 parent studies. Analyses were performed separately for each sample, and results were combined across samples by meta-analysis. Two SNPs (rs2046315 and rs10429371) upstream ofMMP16were significantly associated with caries in an individual sample of white adults and via meta-analysis across 8 adult samples after gene-wise adjustment for multiple comparisons. Noteworthy is SNP rs2046315 (p= 8.14 × 10-8) association with caries in white adults. This SNP was originally nominated in a genome-wide-association study (GWAS) of dental caries in a sample of white adults and yielded associations in a subsequent GWAS of surface level caries in white adults as well. Therefore, in our study, we were able to recapture the association between rs2046315 and dental caries in white adults. Although we did not strengthen evidence thatMMPs 10,14, and16influence caries risk,MMP16is still a likely candidate gene to pursue.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: D D
authors.identifier: 0000-0003-0824-0773
authors.initials: DD
authors.lastname: Lewis
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J R
authors.identifier: 0000-0003-1897-1131
authors.initials: JR
authors.lastname: Shaffer
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, Baltimore, MD, 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 Genomic 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: Psychology, Dental Practice and Rural Health, West Virginia University, Morgantown, WV, USA.
authors.forename: D W
authors.identifier: 0000-0002-0766-8455
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.identifier: 0000-0003-3392-6881
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