Erosive tooth wear is defined as irreversible loss of dental tissues due to intrinsic or extrinsic acids, exacerbated by mechanical forces. Recent studies have suggested a higher prevalence of erosive tooth wear in males, as well as a genetic contribution to susceptibility to erosive tooth wear. Our aim was to examine erosive tooth wear by performing a genome-wide association study (GWAS) in a sample of the Northern Finland Birth Cohort 1966 (n = 1,962). Erosive tooth wear was assessed clinically using the basic erosive wear examination. A GWAS was performed for the whole sample as well as separately for males and females. We identified one genome-wide significant signal (rs11681214) in the GWAS of the whole sample near the genes PXDN and MYT1L. When the sample was stratified by sex, the strongest genome-wide significant signals were observed in or near the genes FGFR1, C8orf86, CDH4, SCD5, F2R, and ING1. Additionally, multiple suggestive association signals were detected in all GWASs performed. Many of the signals were in or near the genes putatively related to oral environment or tooth development, and some were near the regions considered to be associated with dental caries, such as 2p24, 4q21, and 13q33. Replications of these associations in other samples, as well as experimental studies to determine the biological functions of associated genetic variants, are needed.

Alaraudanjoki V, Laitala ML, Tjaderhane L, Pesonen P, Lussi, A, Anttonen V: Association of erosive tooth wear and dental caries in Northern Finland Birth Cohort 1966 – an epidemiological cross-sectional study. BMC Oral Health 2016; 17: 6.
Ashaie MA, Chowdhury EH: Cadherins: the superfamily critically involved in breast cancer. Curr Pharm Des 2016; 22: 616–638.
Bartlett D, Ganss C, Lussi A: Basic erosive wear examination (BEWE): a new scoring system for scientific and clinical needs. Clin Oral Invest 2008; 12: 65–68.
Bellenghi M, Puglisi R, Pedini F, De Feo A, Felicetti F, Bottero L, Sangaletti S, Errico MC, Petrini M, Gesumundo C, Denaro M, Felli N, Pasquini L, Tripodo C, Colombo MP, Carè A, Mattia G: SCD5-induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B. J Pathol 2015; 236: 315–325.
Dallosso AR, Hancock AL, Szemes M, Moorwood K, Chilukamarri L, Tsai HH, Sarkar A, Barasch J, Vuononvirta R, Jones C, Pritchard-Jones K, Royer-Pokora B, Lee SB, Owen C, Malik S, Feng Y, Frank M, Ward A, Brown KW, Malik K: Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms’ tumor. PLoS Genet 2009; 5:e1000745.
De Rocker N, Vergult S, Koolen D, Jacobs E, Hoischen A, Zeesman S, Bang B, Bena F, Bockaert N, Bongers EM, Devriendt K, Giglio S, Faivre L, Joss S, Maas S, Marle N, Novara F, Nowaczyk MJ, Peeters H, Polstra A, Roelens F, Rosenberg C, Thevenon J, Tümer Z, Vanhauwaert S, Varvagiannis K, Willaert A, Willemsen M, Willems M, Zuffardi O, Coucke P, Speleman F, Eichler EE, Kleefstra T, Menten B: Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity. Genet Med 2015; 17: 460–466.
Eckert S, Feingold E, Cooper M, Vanyukov MM, Maher BS, Slayton RL, Willing MC, Reis SE, McNeil DW, Crout RJ, Weyant RJ, Levy SM, Vieira AR, Marazita ML, Shaffer JR: Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries. J Hum Genet 2017; 62: 491–496.
Guan X, Xu M, Millar SE, Bartlett JD: Beta-catenin is essential for ameloblast movement during enamel development. Eur J Oral Sci 2016; 124: 221–227.
Hannig C, Spitzmuller B, Knausenberger S, Hoth-Hannig W, Hellwig E, Hannig M: Detection and activity of peroxidase in the in situ formed enamel pellicle. Arch Oral Biol 2008; 53: 849–858.
Hannig M, Hannig C: The pellicle and erosion. Monogr Oral Sci 2014; 25: 206–214.
Hasselkvist A, Johansson A, Johansson AK: Dental erosion and soft drink consumption in Swedish children and adolescents and the development of a simplified erosion partial recording system. Swed Dent J 2010; 34: 187–195.
Hasselkvist A, Johansson A, Johansson AK: A 4-year prospective longitudinal study of progression of dental erosion associated to lifestyle in 13- to 14-year-old Swedish adolescents. J Dent 2016; 47: 55–62.
Holbrook WP, Furuholm J, Gudmundsson K, Theodors A, Meurman JH: Gastric reflux is a significant causative factor of tooth erosion. J Dent Res 2009; 88: 422–426.
Huang F, Hu X, Fang C, Liu H, Lin C, Zhang Y, Hu X: Expression profile of critical genes involved in FGF signaling pathway in the developing human primary dentition. Histochem Cell Biol 2015; 144: 457–469.
Jeremias F, Pierri RA, Souza JF, Fragelli CM, Restrepo M, Finoti LS, Bussaneli DG, Cordeiro RC, Secolin R, Maurer-Morelli CV, Scarel-Caminaga RM, Santos-Pinto L: Family-based genetic association for molar-incisor hypomineralization. Caries Res 2016; 50: 310–318.
Kaneko M, Alvarez-Manilla G, Kamar M, Lee I, Lee JK, Troupe K, Zhang W, Osawa M, Pierce M: A novel beta(1,6)-N-acetylglucosaminyltransferase V (GnT-VB)(1). FEBS Lett 2003; 554: 515–519.
Kettunen P, Karavanova I, Thesleff I: Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1, -2, -3, and of FGFR4; and stimulation of cell proliferation by FGF-2, -4, -8, and -9. Dev Genet 1998; 22: 374–385.
Küchler EC, Pecharki GD, Castro ML, Ramos J, Barbosa F Jr, Brancher JA, Vieira AR, Gerlach RF, Trevilatto PC: Genes involved in the enamel development are associated with calcium and phosphorus level in saliva. Caries Res 2017; 51: 225–230.
Laajala A, Karhatsu P, Pesonen P, Laitala ML, Näpänkangas R, Raustia A, Anttonen V: Association of indirect restorations with past caries history and present need for restorative treatment in the Northern Finland Birth Cohort 1966. Clin Oral Investig 2018; 22: 1495–1501.
Li CY, Cha W, Luder HU, Charles RP, McMahon M, Mitsiadis TA, Klein OD: E-cadherin regulates the behavior and fate of epithelial stem cells and their progeny in the mouse incisor. Dev Biol 2012; 366: 357–366.
Lochovska K, Peterkova R, Pavlikova Z, Hovorakova M: Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation. BMC Dev Biol 2015; 15: 21.
Mulic A, Tveit AB, Hove LH, Skaare AB: Dental erosive wear among Norwegian wine tasters. Acta Odontol Scand 2011; 69: 21–26.
Nothern Finland Cohorts (Internet). Univeristy of Oulu. 2017.
Peltonen L, Palotie A, Lange K: Use of population isolates for mapping complex traits. Nat Rev Genet 2000; 1: 182–190.
Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, Jones CG, Zaitlen NA, Varilo T, Kaakinen M Sovio U, Ruokonen A, Laitinen J, Jakkula E, Coin L, Hoggart C, Collins A, Turunen H, Gabriel S, Elliot P, McCarthy MI, Daly MJ, Järvelin MR, Freimer NB, Peltonen L: Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 2009; 41: 35–46.
Salas MM, Nascimento GG, Vargas-Ferreira F, Tarquinio SB, Huysmans MC, Demarco FF: Diet influenced tooth erosion prevalence in children and adolescents: results of a meta-analysis and meta-regression. J Dent 2015; 43: 865–875.
Schlueter N, Ganss C, Pötschke S, Klimek J, Hannig C: Enzyme activities in the oral fluids of patients suffering from bulimia: a controlled clinical trial. Caries Res 2012: 46: 130–139.
Shaffer JR, Feingold E, Wang X, Lee M, Tcuenco K, Weeks DE, Weyant RJ, Crout R, McNeil DW, Marazita ML; GWAS of dental caries patterns in the permanent dentition. J Dent Res 2013; 92: 38–44.
Shimizu T, Deeley K, Briseno-Ruiz J, Faraco IM Jr, Poletta FA, Brancher JA, Pecharki GD, Küchler EC, Tannure PN, Lips A, Vieira TC, Patir A, Yildirim M, Mereb JC, Resick JM, Brandon CA, Cooper ME, Seymen F, Costa MC, Granjeiro JM, Trevilatto PC, Orioli IM, Castilla EE, Marazita ML, Vieira AR: Fine-mapping of 5q12.1–13.3 unveils new genetic contributors to caries. Caries Res 2013; 47: 273–283.
Simmer JP, Richardson AS, Wang SK, Reid BM, Bai Y, Hu Y, Hu JC: Ameloblast transcriptome changes from secretory to maturation stages. Connect Tissue Res 2014; 55: 29–32.
Sinner DI, Kim GJ, Henderson GC, Igal RA: StearoylCoA desaturase-5: a novel regulator of neuronal cell proliferation and differentiation. PLoS One 2012; 7:e39787.
Søvik JB, Vieira AR, Tveit AB, Mulic A: Enamel formation genes associated with dental erosive wear. Caries Res 2015a; 49: 236–242.
Søvik JB, Skudutyte-Rysstad R, Tveit AB, Sandvik L, Mulic A: Sour sweets and acidic beverage consumption are risk indicators for dental erosion. Caries Res 2015b; 49: 243–250.
Stevens SJ, van Ravenswaaij-Arts CM, Janssen JW, Klein Wassink-Ruiter JS, van Essen AJ, Dijkhuizen T, van Rheenen J, Heuts-Vijgen R, Stegmann AP, Smeets EE, Engelen JJ: MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Am J Med Genet A 2011; 155A: 2739–2745.
Suryadeva S, Khan MB: Role of homeobox genes in tooth morphogenesis: a review. J Clin Diagn Res 2015; 9:ZE09–ZE12.
Taji SS, Seow WK, Townsend GC, Holcombe T: A controlled study of dental erosion in 2- to 4-year-old twins. Int J Paediatr Dent 2010; 20: 400–409.
Takamori K, Hosokawa R, Xu X, Deng X, Bringas P Jr, Chai Y: Epithelial fibroblast growth factor receptor 1 regulates enamel formation. J Dent Res 2008; 87: 238–243.
Thesleff I, Keranen S, Jernvall J: Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation. Adv Dent Res 2001; 15: 14–18.
Tschammler C, Muller-Pflanz C, Attin T, Muller J, Wiegand A: Prevalence and risk factors of erosive tooth wear in 3–6 year old German kindergarten children – a comparison between 2004/05 and 2014/15. J Dent 2016; 52: 45–49.
Tye CE, Lorenz RL, Bartlett JD: Lysosomal protease expression in mature enamel. Cells Tissues Organs 2009; 189: 111–114.
Uhlen MM, Mulic A, Holme B, Tveit AB, Stenhagen KR: The susceptibility to dental erosion differs among individuals. Caries Res 2016a; 50: 117–123.
Uhlen MM, Stenhagen KR, Dizak PM, Holme B, Mulic A, Tveit AB, Vieira AR: Genetic variation may explain why females are less susceptible to dental erosion. Eur J Oral Sci 2016b; 124: 426–432.
Vidal CM, Tjaderhane L, Scaffa PM, Tersariol IL, Pashley D, Nader HB, Nascimento FD, Carrilho MR: Abundance of MMPs and cysteine cathepsins in caries-affected dentin. J Dent Res 2014; 93: 269–274.
Woo Seo D, Yeop You S, Chung WJ, Cho DH, Kim JS, Su Oh J: Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis. Sci Rep 2015; 5: 15431.
Xie J, Feng Y, Lin T, Huang XY, Gan RH, Zhao Y, Su BH, Ding LC, She L, Chen J, Lin LS, Lin X, Zheng DL, Lu YG: CDH4 suppresses the progression of salivary adenoid cystic carcinoma via E-cadherin co-expression. Oncotarget 2016; 7: 82961–82971.
Yamakoshi Y, Yamakoshi F, Hu JC, Simmer JP: Characterization of kallikrein-related peptidase 4 glycosylations. Eur J Oral Sci 2011; 119: 234–240.
Zhang R, Jin J, Shi J, Hou Y: INGs are potential drug targets for cancer. J Cancer Res Clin Oncol 2017; 143: 189–197.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.