Top

Published in:

01-03-2014 | Short Communication

Genome-wide association study (GWAS) for molar–incisor hypomineralization (MIH)

Authors: Jan Kühnisch, Elisabeth Thiering, Daniela Heitmüller, Carla M. T. Tiesler, Harald Grallert, Roswitha Heinrich-Weltzien, Reinhard Hickel, Joachim Heinrich, The GINI-10 plus study group, The LISA-10 plus study group

Published in: Clinical Oral Investigations | Issue 2/2014

Abstract

Objectives

This genome-wide association study (GWAS) investigated the relationship between molar–incisor hypomineralization (MIH) and possible genetic loci. Clinical and genetic data from the 10-year follow-up of 668 children from the Munich GINI-plus and LISA-plus birth cohort studies were analyzed.

Material and methods

The dental examinations included the diagnosis of MIH according to the criteria of the European Academy of Paediatric Dentistry (EAPD). Children with MIH were categorized as those with a minimum of one hypomineralized first permanent molar. A GWAS was implemented following a quality-control step and an additive genetic effect was assumed.

Results

A total of 2,013,491 single-nucleotide polymorphisms (SNPs) were available for analysis. Rs13058467, which is located near the SCUBE1 gene on chromosome 22 (p < 3.72E-7), was identified as a possible locus linked to MIH when using a threshold of p value <1E-6.

Conclusions

After considering the limitations of the present study (e.g., limited sample size and lack of an independent replication sample), it can be concluded that (1) replication analyses in an independent cohort study are strongly recommended and (2) large-scale and well-powered studies are needed to investigate a possible genetic link to MIH.

Available only for authorised users

Crombie F, Manton D, Kilpatrick N (2009) Aetiology of molar–incisor hypomineralization: a critical review. Int J Paediatr Dent 19:73–83PubMedCrossRef

Alaluusua S (2010) Aetiology of molar–incisor hypomineralisation: a systematic review. Eur Arch Paediatr Dent 11:53–58PubMedCrossRef

Kühnisch J, Heitmüller D, Thiering E, Brockow I, Hoffmann U, Neumann C, Heinrich-Weltzien R, Bauer CP, von Berg A, Koletzko S, Garcia-Godoy F, Hickel R, Heinrich J (2012) Prevalence and extent of manifestation of molar–incisor hypomineralisations according to different phenotypes. J Public Health Dent. doi:10.1111/j.1365-263X.2012.01233.x PubMed

Jälevik B (2010) Prevalence and diagnosis of molar–incisor hypomineralization (MIH): a systematic review. Eur Arch Paediatr Dent 11:59–64PubMedCrossRef

Dietrich G, Sperling S, Hetzer G (2003) Molar incisor hypomineralization in a group of children and adolescents living in Dresden (Germany). Eur J Paediatr Dent 4:133–137PubMed

Preusser SE, Ferring V, Wleklinski C, Wetzel WE (2007) Prevalence and severity of molar incisor hypomineralization in a Region of Germany—a brief communication. J Public Health Dent 67:148–150PubMedCrossRef

Matalova E, Fleischmannova J, Sharpe PT, Tucker AS (2008) Tooth agenesis: from molecular genetics to molecular dentistry. J Dent Res 87:617–623PubMedCrossRef

Tucker A, Sharpe P (2004) The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5:499–508PubMedCrossRef

Tucker AS, Sharpe PT (1999) Molecular genetics of tooth morphogenesis and patterning: the right shape in the right place. J Dent Res 78:826–834PubMedCrossRef

10.

Heinrich J, Bolte G, Hölscher B, Douwes J, Lehmann I, Fahlbusch B, Bischof W, Weiss M, Borte M, Wichmann HE, LISA Study Group (2002) Allergens and endotoxin on mothers’ mattresses and total immunoglobulin E in cord blood of neonates. Eur Respir J 20:617–663PubMedCrossRef

11.

von Berg A, Filipiak-Pittroff B, Krämer U, Link E, Bollrath C, Brockow I, Koletzko S, Grübl A, Heinrich J, Wichmann HE, Bauer CP, Reinhardt D, Berdel D, GINIplus study group (2008) Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). J Allergy Clin Immunol 121:1442–1447PubMedCrossRef

12.

Heinrich J, Brüske I, Schnappinger M, Standl M, Flexeder C, Thiering E, Tischer C, Tiesler CM, Kohlböck G, Wenig CM, Bauer CP, Schaaf B, von Berg A, Berdel D, Krämer U, Cramer C, Lehmann I, Herbarth O, Behrendt H, Ring J, Kühnisch J, Koletzko S (2012) Two German birth cohorts: GINIplus and LISAplus. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55:864–874PubMedCrossRef

13.

Weerheijm KL, Duggal M, Mejare I, Papagiannoulis KG, Martens LC, Hallonsten AL (2003) Judgement criteria for molar incisor hypomineralisation (MIH) in epidemiologic studies: a summary of the European meeting on MIH held in Athens, 2003. Eur J Paediatr Dent 4:110–113PubMed

14.

Lygidakis NA, Wong F, Jälevik B, Vierrou A, Alaluusua S, Espelid I (2010) Best clinical practice guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH). An EAPD policy document. Eur Arch Paediatr Dent 11:75–81PubMedCrossRef

15.

Heitmüller D, Thiering E, Neumann C, Hoffmann U, Bauer CP, Heinrich-Weltzien R, Manton D, Hickel R, Heinrich J, Kühnisch J, the GINIplus Study Group (2012) Is there a positive relationship between Molar Incisor Hypomineralisations and the presence of dental caries. Int J Paediatr Dent. doi:10.1111/j.1752-7325.2012.00365.x PubMed

16.

The International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796CrossRef

17.

Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) Locus Zoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336–2337PubMedCentralPubMedCrossRef

18.

Pe’er I, Yelensky R, Altshuler D, Daly MJ (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32:381–385PubMedCrossRef

19.

Xavier GM, Sharpe PT, Cobourne MT (2009) Scube1 is expressed during facial development in the mouse. J Exp Zool (Mol Dev Evol) 312B:518–524CrossRef

20.

Tu CF, Yan YT, Wu SY, Djoko B, Tsai MT, Cheng CJ, Yang RB (2008) Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE1. J Biol Chem 283:12478–12488PubMedCrossRef

21.

Aberg T, Wozney J, Thesleff I (1997) Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev Dyn 210:383–396PubMedCrossRef

22.

Helder MN, Karg H, Bervoets TJ, Vukicevic S, Burger EH, D’Souza RN, Woltgens JH, Karsenty G, Bronckers AL (1998) Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development. J Dent Res 77:545–554PubMedCrossRef

23.

Vainio S, Karavanova I, Jowett A, Thesleff I (1993) Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75:45–58PubMedCrossRef

24.

Thesleff I (2006) The genetic basis of tooth development and dental defects. Am J Med Genet A 140:2530–2535PubMedCrossRef

25.

Bailleul-Forestier I, Molla M, Verloes A, Berdal A (2008) The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders. Eur J Med Genet 51:273–291PubMedCrossRef

26.

Bailleul-Forestier I, Berdal A, Vinckier F, de Ravel T, Fryns JP, Verloes A (2008) The genetic basis of inherited anomalies of the teeth. Part 2: syndromes with significant dental involvement. Eur J Med Genet 51:383–408PubMedCrossRef

27.

Shaffer JR, Wang X, Desensi RS, Wendell S, Weyant RJ, Cuenco KT, Crout R, McNeil DW, Marazita ML (2012) Genetic susceptibility to dental caries on pit and fissure and smooth surfaces. Caries Res 46:38–46PubMedCentralPubMedCrossRef

28.

Shaffer JR, Wang X, Feingold E, Lee M, Begum F, Weeks DE, Cuenco KT, Barmada MM, Wendell SK, Crosslin DR, Laurie CC, Doheny KF, Pugh EW, Zhang Q, Feenstra B, Geller F, Boyd HA, Zhang H, Melbye M, Murray JC, Weyant RJ, Crout R, McNeil DW, Levy SM, Slayton RL, Willing MC, Broffitt B, Vieira AR, Marazita ML (2011) Genome-wide association scan for childhood caries implicates novel genes. J Dent Res 90:1457–1462PubMedCentralPubMedCrossRef

29.

Wang X, Shaffer JR, Zeng Z, Begum F, Vieira AR, Noel J, Anjomshoaa I, Cuenco KT, Lee MK, Beck J, Boerwinkle E, Cornelis MC, Hu FB, Crosslin DR, Laurie CC, Nelson SC, Doheny KF, Pugh EW, Polk DE, Weyant RJ, Crout R, McNeil DW, Weeks DE, Feingold E, Marazita ML (2012) Genome-wide association scan of dental caries in the permanent dentition. BMC Oral Health. doi:10.1186/1472-6831-12-57

30.

Gauderman W, Morrison J (2006) QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydra.usc.edu/gxe.

Title: Genome-wide association study (GWAS) for molar–incisor hypomineralization (MIH)
Authors: Jan Kühnisch
Elisabeth Thiering
Daniela Heitmüller
Carla M. T. Tiesler
Harald Grallert
Roswitha Heinrich-Weltzien
Reinhard Hickel
Joachim Heinrich
The GINI-10 plus study group
The LISA-10 plus study group
Publication date: 01-03-2014
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 2/2014
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-013-1054-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genome-wide association study (GWAS) for molar–incisor hypomineralization (MIH)

Abstract

Objectives

Material and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Material and methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2014

Adhesive restoration of anterior endodontically treated teeth: influence of post length on fracture strength

Radiologic bone loss in patients with bisphosphonate-associated osteonecrosis of the jaws: a case–control study

The 100 most cited articles in dentistry—some discussions

Periodontal intraligament injection as alternative to inferior alveolar nerve block—meta-analysis of the literature from 1979 to 2012

Comparison of the effect of two sugar-substituted chewing gums on different caries- and gingivitis-related variables: a double-blind, randomized, controlled clinical trial

Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects