Validation of reported genetic risk factors for periodontitis in a large-scale replication study

Authors


  • Conflict of interest and source of funding statement

    This study was supported by the German Ministry of Education and Research (BMBF) through National Genome Research Network (NGFN) grants (Michael Nothnagel, 01GS0809, Thomas Manke TM 01GS1110,), by a grant of the Deutsche Forschungsgemeinschaft (KFO208) (Arne S. Schaefer), by a research grant of the “Research Center Inflammation Medicine” of the Medical Faculty, Christian-Albrechts-University, University Medical Center Schleswig-Holstein, Campus Kiel, (Gregor Bochenek), by the German Ministry of Education and Research through the POPGEN biobank project (01GR0468), by a grant from BONFOR of the Medical Faculty, University of Bonn (Søren Jepsen), by a grant from the ARPA Research Foundation (Søren Jepsen), Regensburg, Germany, and in part by a grant of the University of Amsterdam for the focal point “Oral Infections and Inflammation” (Bruno G. Loos). The authors declare that they have no conflict of interests.

  • This study was awarded with the EFP-Jaccard Research Prize 2012.

Address:

Arne S. Schaefer, Christian-Albrechts- University, Institute for Clinical Molecular Biology, Schittenhelmstrasse 12, 24105 Kiel, Germany

E-mail: a.schaefer@ikmb.uni-kiel.de

Abstract

Aim

Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP).

Material and Methods

We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population.

Results

None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6–0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11–2.60]).

Conclusions

Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.

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