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

M. Munz; H. Chen; Y. Jockel-Schneider; K. Adam; P. Hoffman; K. Berger; T. Kocher; J. Meyle; P. Eickholz; C. Doerfer; M. Laudes; A. Uitterlinden; W. Lieb; A. Franke; S. Schreiber; S. Offenbacher; K. Divaris; C. Bruckmann; B.G. Loos; S. Jepsen; H. Dommisch; A.S. Schäefer

doi:10.1111/jcpe.12749

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

M. Munz, H. Chen, Y. Jockel-Schneider, K. Adam, P. Hoffman, K. Berger, T. Kocher, J. Meyle, P. Eickholz, C. Doerfer, M. Laudes, A. Uitterlinden, W. Lieb, A. Franke, S. Schreiber, S. Offenbacher, K. Divaris, C. Bruckmann, B.G. Loos, S. JepsenH. Dommisch, A.S. Schäefer

Periodontology

Research output: Contribution to Journal › Article › Academic › peer-review

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
Pages (from-to)	962-970
Journal	Journal of Clinical Periodontology
Volume	44
Issue number	10
DOIs	https://doi.org/10.1111/jcpe.12749
Publication status	Published - 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.

Funders	Funder number
Federal Ministry of Education and Research BMBF	FKZ 0315540A
German Centre for Neurodegenerative Disorders
German Migraine & Headache Society
University of Muenster
Pfizer
Merck Sharp and Dohme
Deutsche Forschungsgemeinschaft	SCHA 1582/3-1, ER 155/6-1, SI 236/8-1, SI236/9-1
Bundesministerium für Bildung und Forschung
Deutsches Zentrum für Neurodegenerative Erkrankungen
Deutsche Migräne- und Kopfschmerzgesellschaft e.V.
Heinz Nixdorf Stiftung

UN SDGs

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

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10.1111/jcpe.12749

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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, 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{6710f6d19eb448a7896a27e96c6a441a,

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

abstract = "AimThe 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 MethodsThe 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. ResultsRs4252120 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). ConclusionsOur findings support a role of genetic variants in PLG in the aetiology of periodontitis. ",

author = "M. Munz and H. Chen and Y. Jockel-Schneider and K. Adam and P. Hoffman and K. Berger and T. Kocher and J. Meyle and P. Eickholz and C. Doerfer and M. Laudes and A. Uitterlinden and W. Lieb and A. Franke and S. Schreiber and S. Offenbacher and K. Divaris and C. Bruckmann and B.G. Loos and S. Jepsen and H. Dommisch and A.S. Sch{\"a}efer",

year = "2017",

doi = "10.1111/jcpe.12749",

language = "English",

volume = "44",

pages = "962--970",

journal = "Journal of Clinical Periodontology",

issn = "0303-6979",

publisher = "Blackwell Munksgaard",

number = "10",

}

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, M.

AU - Chen, H.

AU - Jockel-Schneider, Y.

AU - Adam, K.

AU - Hoffman, P.

AU - Berger, K.

AU - Kocher, T.

AU - Meyle, J.

AU - Eickholz, P.

AU - Doerfer, C.

AU - Laudes, M.

AU - Uitterlinden, A.

AU - Lieb, W.

AU - Franke, A.

AU - Schreiber, S.

AU - Offenbacher, S.

AU - Divaris, K.

AU - Bruckmann, C.

AU - Loos, B.G.

AU - Jepsen, S.

AU - Dommisch, H.

AU - Schäefer, A.S.

PY - 2017

Y1 - 2017

N2 - AimThe 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 MethodsThe 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. ResultsRs4252120 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). ConclusionsOur findings support a role of genetic variants in PLG in the aetiology of periodontitis.

AB - AimThe 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 MethodsThe 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. ResultsRs4252120 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). ConclusionsOur findings support a role of genetic variants in PLG in the aetiology of periodontitis.

U2 - 10.1111/jcpe.12749

DO - 10.1111/jcpe.12749

M3 - Article

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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