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

Arne S Schaefer, Gregor Bochenek, Thomas Manke, Michael Nothnagel, Christian Graetz, Anneke Thien, Yvonne Jockel-Schneider, Inga Harks, Ingmar Staufenbiel, Cisca Wijmenga, Jörg Eberhard, Esra Guzeldemir-Akcakanat, Naci Cine, Mathias Folwaczny, Barbara Noack, Joerg Meyle, Peter Eickholz, Leonardo Trombelli, Chiara Scapoli, Rahime Nohutcu, Corinna Bruckmann, Christof Doerfer, Søren Jepsen, Bruno G Loos, Stefan Schreiber
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Journal of clinical periodontology
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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).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.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]).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.