Complex analysis of multiple single nucleotide polymorphisms as putative risk factors of tooth agenesis in the Hungarian population. (April 2014)

• Record Type: Journal Article
• Authors: Jobbágy-Óvári, Gabriella; Páska, Csilla; Stiedl, Péter; Trimmel, Bálint; Hontvári, Dorina; Soós, Borbála; Hermann, Péter; Tóth, Zsuzsanna; Kerekes-Máthé, Bernadette; Nagy, Dávid; Szántó, Ildikó; Nagy, Ákos; Martonosi, Mihály; Nagy, Katalin; Hadadi, Éva; Szalai, Csaba; Hullám, Gábor; Temesi, Gergely; Antal, Péter; Varga, Gábor; Tarján, IldIkó
• Is Part Of: Acta odontologica Scandinavica. Volume 72:Number 3(2014)
• Page Start: 216
• Page End: 227
• Publication Date: 2014-04
• Subjects: Dentistry -- Periodicals; 617.6005
• DOI: 10.3109/00016357.2013.822547
• Languages: English
• ISSNs: 0001-6357

Abstract

<abstract> <title>Abstract</title> <p> <bold> <italic>Objectives.</italic> </bold> The role was studied of multiple single nucleotide polymorphisms in tooth agenesis in the Hungarian population using a complex approach. <bold><italic>Methods.</italic></bold> Eight SNPs, <italic>PAX9</italic> -912 C/T, <italic>PAX9</italic> -1031 A/G, <italic>MSX1</italic> 3755 A/G, <italic>FGFR1</italic> T/C rs881301, <italic>IRF6</italic> T/C rs764093, <italic>AXIN2</italic>-8150 A/G, <italic>AXIN2</italic>-8434 A/G and <italic>AXIN2</italic>-30224 C/T, were studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers. Case-control analysis was performed to test both allelic and genotypic associations as well as associations at the level of haplotypes. Multivariate exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as well as logistic regression analysis were performed. <bold><italic>Results.</italic></bold> Conventional statistics showed that <italic>PAX9</italic> SNP -912 C/T and the <italic>MSX1</italic> SNP changed the incidence of hypodontia, although after Bonferroni correction for multiple hypothesis testing, the effects were only borderline tendencies. Using a statistical analysis better suited for handling multiple hypotheses, the BN-BMLA, <italic>PAX9</italic> SNPs clearly showed a synergistic effect. This was confirmed by other multivariate analyses and it remained significant after corrections for multiple hypothesis testing (<italic>p</italic> < 0.0025). The <italic>PAX9</italic>-1031-A-<italic>PAX9-</italic>912-T haplotype was the most relevant combination causing hypodontia. Interaction was weaker between <italic>PAX9</italic> and <italic>MSX1, </italic> while other SNPs had no joint effect on hypodontia. <bold><italic>Conclusion.</italic></bold> This complex analysis shows the important role of <italic>PAX9</italic> and <italic>MSX1</italic> SNPs and of their interactions in tooth agenesis, while <italic>IRF6, </italic><italic>FGFR1</italic> and <italic>AXIN2</italic> SNPs had no detectable role in the Hungarian population. These results also reveal that risk factors in hypodontia need to be identified in various populations, since there is considerable variability among them.</p> </abstract>