A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis.

Matthias Munz, Hong Chen, Yvonne Jockel-Schneider, Knut Adam, Per Hoffman, Klaus Berger, Thomas Kocher, Jörg Meyle, Peter Eickholz, Christof Doerfer, Matthias Laudes, André Uitterlinden, Wolfgang Lieb, Andre Franke, Stefan Schreiber, Steven Offenbacher, Kimon Divaris, Corinna Bruckmann, Bruno G Loos, Soeren Jepsen, Henrik Dommisch, Arne S Schaefer
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Journal of clinical periodontology
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The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP.The association of PLG candidate rs4252120 was tested in a German case-control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases (N=851) and controls (N=6,836) were genotyped with HumanOmni BeadChips. The North-American CP sample (N=2,681 cases, 1,823 controls) was previously genotyped on the Genome-Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2) and association tests were performed using an additive genetic model adjusting for sex and smoking.Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r(2) =0.08) was associated with both AgP (rs1247559; P=0.002, odds ratio [OR]=1.33) and CP (P=0.02, OR=1.15). That locus was also significantly associated with PLG expression in osteoblasts (p=6.9x10(-5) ).Our findings support a role of genetic variants in PLG in the etiology of periodontitis. This article is protected by copyright. All rights reserved.