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

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 JepsenHenrik Dommisch, Arne S. Schäefer^*

^*Corresponding author for this work

20 Citations (Scopus)

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.

Original language	English
Journal	Journal of Clinical Periodontology
Volume	44
Issue number	10
Pages (from-to)	962-970
Number of pages	9
ISSN	0303-6979
DOIs	https://doi.org/10.1111/jcpe.12749
Publication status	Published - 01.10.2017

Funding

This study was supported by a research grant of the Deutsche Forschungsgemeinschaft DFG (GZ: SCHA 1582/3-1). The Dortmund Health Study (DOGS) is supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme, and Pfizer to the University of Muenster (collection of sociodemographic and clinical data). Blood collection in the Dortmund Health Study was carried out through funds from the Institute of Epidemiology and Social Medicine University of Muenster. FOCUS was supported by the Federal Ministry of Education and Research BMBF (FKZ 0315540A). The HNR study is supported by the Heinz Nixdorf Foundation (Germany). Additionally, the study is funded by the German Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). The genotyping of the Illumina HumanOmni-1 Quad BeadChips of the HNR subjects was financed by the German Centre for Neurodegenerative Disorders (DZNE), Bonn.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jcpe.12749

Cite this

Munz, M., Chen, H., Jockel-Schneider, Y., Adam, K., Hoffman, P., Berger, K., Kocher, T., Meyle, J., Eickholz, P., Doerfer, C., Laudes, M., Uitterlinden, A., Lieb, W., Franke, A., Schreiber, S., Offenbacher, S., Divaris, K., Bruckmann, C., Loos, B. G., ... Schäefer, A. S. (2017). A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis. Journal of Clinical Periodontology, 44(10), 962-970. https://doi.org/10.1111/jcpe.12749

@article{78dbd5e56ebe4fdab1cc3075d1ad3f7a,

title = "A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis",

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.",

author = "Matthias Munz and Hong Chen and Yvonne Jockel-Schneider and Knut Adam and Per Hoffman and Klaus Berger and Thomas Kocher and J{\"o}rg Meyle and Peter Eickholz and Christof Doerfer and Matthias Laudes and Andr{\'e} Uitterlinden and Wolfgang Lieb and Andre Franke and Stefan Schreiber and Steven Offenbacher and Kimon Divaris and Corinna Bruckmann and Loos, \{Bruno G.\} and S{\o}eren Jepsen and Henrik Dommisch and Sch{\"a}efer, \{Arne S.\}",

year = "2017",

month = oct,

day = "1",

doi = "10.1111/jcpe.12749",

language = "English",

volume = "44",

pages = "962--970",

journal = "Journal of Clinical Periodontology",

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Munz, M, Chen, H, Jockel-Schneider, Y, Adam, K, Hoffman, P, Berger, K, Kocher, T, Meyle, J, Eickholz, P, Doerfer, C, Laudes, M, Uitterlinden, A, Lieb, W, Franke, A, Schreiber, S, Offenbacher, S, Divaris, K, Bruckmann, C, Loos, BG, Jepsen, S, Dommisch, H & Schäefer, AS 2017, 'A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis', Journal of Clinical Periodontology, vol. 44, no. 10, pp. 962-970. https://doi.org/10.1111/jcpe.12749

TY - JOUR

T1 - A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis

AU - Munz, Matthias

AU - Chen, Hong

AU - Jockel-Schneider, Yvonne

AU - Adam, Knut

AU - Hoffman, Per

AU - Berger, Klaus

AU - Kocher, Thomas

AU - Meyle, Jörg

AU - Eickholz, Peter

AU - Doerfer, Christof

AU - Laudes, Matthias

AU - Uitterlinden, André

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Schreiber, Stefan

AU - Offenbacher, Steven

AU - Divaris, Kimon

AU - Bruckmann, Corinna

AU - Loos, Bruno G.

AU - Jepsen, Søeren

AU - Dommisch, Henrik

AU - Schäefer, Arne S.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85029211366

U2 - 10.1111/jcpe.12749

DO - 10.1111/jcpe.12749

M3 - Journal articles

AN - SCOPUS:85029211366

SN - 0303-6979

VL - 44

SP - 962

EP - 970

JO - Journal of Clinical Periodontology

JF - Journal of Clinical Periodontology

IS - 10

ER -

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

Abstract

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Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis

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

Abstract

Funding

UN SDGs

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Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis

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