title: Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries.
abstract: Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Ida
authors.initials: I
authors.lastname: Anjomshoaa
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Briseño-Ruiz
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Deeley
authors.affiliation: ECLAMC (Latin American Collaborative Study of Congenital Malformations) at CEMIC (Center for Medical Education and Clinical Research), Buenos Aires, Argentina.
authors.forename: Fernardo A
authors.initials: FA
authors.lastname: Poletta
authors.affiliation: ECLAMC at Hospital de Area El Bolson, El Bolson, RN, Argentina.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mereb
authors.affiliation: Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Aline L
authors.initials: AL
authors.lastname: Leite
authors.affiliation: Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Priscila A T M
authors.initials: PA
authors.lastname: Barreta
authors.affiliation: Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Thelma L
authors.initials: TL
authors.lastname: Silva
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Piper
authors.initials: P
authors.lastname: Dizak
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ruff
authors.affiliation: Department of Pedodontics, Medipol Istanbul University, Istanbul, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Patir
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Koruyucu
authors.affiliation: Department of Pediatric Dentistry, Yeditepe University, Faculty of Dentistry, Istanbul, Turkey.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Abbasoğlu
authors.affiliation: Dental School, Clinical Research Unit, Federal Fluminense University - UFF, Niterói, RJ, Brazil.|Biology Institute, Federal Fluminense University - UFF, Niterói, RJ, Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Casado
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Samer H
authors.initials: SH
authors.lastname: Zaky
authors.affiliation: Department of Pedodontics, Medipol Istanbul University, Istanbul, Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Bayram
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Küchler
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.affiliation: Department of Pediatric Dentistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey.
authors.forename: İlknur
authors.initials: İ
authors.lastname: Tanboğa
authors.affiliation: Dental School, Clinical Research Unit, Federal Fluminense University - UFF, Niterói, RJ, Brazil.|National Institute of Metrology (INMETRO), Niterói, RJ, Brazil.
authors.forename: José M
authors.initials: JM
authors.lastname: Granjeiro
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Seymen
authors.affiliation: ECLAMC (Latin American Collaborative Study of Congenital Malformations) at CEMIC (Center for Medical Education and Clinical Research), Buenos Aires, Argentina.|ECLAMC at INAGEMP-CNPq (National Institute of Population Medical Genetics) at Department of Genetics, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.affiliation: ECLAMC at INAGEMP-CNPq (National Institute of Population Medical Genetics) at Department of Genetics, Institute of Biology, Center of Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Iêda M
authors.initials: IM
authors.lastname: Orioli
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Sfeir
authors.affiliation: Department of Pediatric Dentistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey.
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Owyang
authors.affiliation: Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Marília A R
authors.initials: MA
authors.lastname: Buzalaf
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D003731:Dental Caries / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005459:Fluorides / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042361:Mammary Glands, Human / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000378:metabolism; D055815:Young Adult
chemical_list: D051402:Aquaporin 5; D005819:Genetic Markers; D005459:Fluorides