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; Søeren Jepsen; Henrik Dommisch; Arne S Schäefer

doi:10.1111/jcpe.12749

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

J Clin Periodontol. 2017 Oct;44(10):962-970. doi: 10.1111/jcpe.12749. Epub 2017 Sep 11.

Authors

Matthias Munz^{1

2}, Hong Chen^{1

3}, Yvonne Jockel-Schneider⁴, Knut Adam⁵, Per Hoffman^{6

7}, Klaus Berger⁸, Thomas Kocher⁹, Jörg Meyle¹⁰, Peter Eickholz¹¹, Christof Doerfer¹², Matthias Laudes¹³, André Uitterlinden¹⁴, Wolfgang Lieb¹⁵, Andre Franke¹⁶, Stefan Schreiber¹⁶, Steven Offenbacher¹⁷, Kimon Divaris^{18

19}, Corinna Bruckmann²⁰, Bruno G Loos²¹, Søeren Jepsen²², Henrik Dommisch¹, Arne S Schäefer¹

Affiliations

¹ Department of Periodontology, Institute of Dental, Oral and Maxillary Medicine, Charité - University Medicine Berlin, Berlin, Germany.
² Institute for Integrative and Experimental Genomics, University Medical Center Schleswig-Holstein - Campus Lübeck, Lübeck, Germany.
³ Department of Stomatology, Zhejiang Provincial People's Hospital, Hangzhou, China.
⁴ Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Würzburg, Germany.
⁵ Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany.
⁶ Institute of Human Genetics, University of Bonn, Bonn, Germany.
⁷ Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland.
⁸ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
⁹ Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pedodontics, Dental School, University Medicine Greifswald, Greifswald, Germany.
¹⁰ Department of Periodontology, University Medical Center Giessen and Marburg, Gießen, Germany.
¹¹ Department of Periodontology, Centre for Dental, Oral Medicine (Carolinum), Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
¹² Department of Operative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
¹³ Clinic of Internal Medicine I, University Clinic Schleswig-Holstein, Kiel, Germany.
¹⁴ Erasmus Medical Centre, Rotterdam, The Netherlands.
¹⁵ Institute of Epidemiology, Biobank PopGen, Christian-Albrechts-University, Kiel, Germany.
¹⁶ Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
¹⁷ Department of Periodontology, UNC School of Dentistry, Chapel Hill, NC, USA.
¹⁸ Department of Pediatric Dentistry, UNC School of Dentistry, Chapel Hill, NC, USA.
¹⁹ Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA.
²⁰ Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Vienna, Austria.
²¹ Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
²² Department of Periodontology, Operative and Preventive Dentistry, Center of Dento-Maxillo-Facial Medicine Rheinische-Friedrich-Wilhelms-University Bonn, Bonn, Germany.

PMID: 28548211
DOI: 10.1111/jcpe.12749

Abstract

Aim: 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.

Materials and methods: 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.

Results: Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r² = .08) was associated with both AgP (rs1247559; p = .002, odds ratio [OR] = 1.33) and CP (p = .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts (p = 6.9 × 10^-5 ).

Conclusions: Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.

Keywords: aggressive periodontitis; chronic periodontitis; genetic association; plasmin; plasminogen; rs1247559; rs4252120.

MeSH terms

Adult
Aggressive Periodontitis / genetics*
Alleles
Case-Control Studies
Chronic Periodontitis / genetics*
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Germany
Haplotypes / genetics*
Humans
Introns / genetics
Male
Netherlands
North America
Phenotype
Plasminogen / genetics*
Polymorphism, Single Nucleotide*

Substances

Plasminogen