Abstract
Myeloperoxidase (MPO) is an oxidative enzyme expressed in polymorphonuclear leukocytes. It is involved in the defence against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in periodontal disease. A G/A polymorphism in the promoter region of the MPO gene at position −463 has been assumed to exert profound effects on the expression of the enzyme. It is the aim of this study to evaluate whether this polymorphism may influence the risk of periodontal diseases. A total of 3148 subjects were randomly selected from the general population in the SHIP study (Study of Health in Pomerania). Periodontal status, health-related and socio-economic items were assessed. All subjects aged 40–60 years (n = 1103) were included in this study, and 1083 genotyped for the MPO −463 G/A polymorphism by PCR and RFLP methods. The genotype frequencies determined were homozygous wild type G/G 65.9% (95% CI 63.5–68.6), heterozygous A/G 31.4% (28.8–34.4), and homozygous variant A/A 2.7% (2.0–3.8). Only female subjects have a significantly reduced risk of severe periodontal disease when bearing the variant genotypes A/G or A/A. In female subjects the reduction in periodontal risk was significant for non-smokers (OR = 0.48; 95% CI 0.23–0.96); the smoke-related increase in risk was also reduced (OR = 0.50; 95% CI 0.22–1.10). When adjusted for age, smoking, and education the odds ratios were calculated as 0.52 (P = 0.01) and 0.97 (P = 0.90) for female and male subjects, respectively. The results of this study confirm the assumption that the MPO −463A allele variants are protective in the pathogenesis of periodontal diseases. This holds true only with women but not with men. The results are discussed with respect to the known influences of sexual hormones on MPO activity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Miyasaki KT, Nemirovskiy E . Myeloperoxidase isoform activities released by human neutrophils in response to dental and periodontal bacteria Oral Microbiol Immunol 1997 12: 27–32
Cao CF, Smith QT . Crevicular fluid myeloperoxidase at healthy, gingivitis and periodontitis sites J Clin Periodontol 1989 16: 17–20
Altman LC, Baker C, Fleckman P, Luchtel D, Oda D . Neutrophil-mediated damage to human gingival epithelial cells J Periodontal Res 1992 27: 70–79
Eley BM, Cox SW . Advances in periodontal diagnosis. 7. Proteolytic and hydrolytic enzymes link with periodontitis Br Dent J 1998 184: 323–328
Hofstra AH, Uetrecht JP . Myeloperoxidase-mediated activation of xenobiotics by human leukocytes Toxicology 1993 82: 221–242
Uetrecht JP, Shear NH, Zahid N . N-chlorination of sulfamethoxazole and dapsone by the myeloperoxidase system Drug Metab Dispos 1993 21: 830–834
Trush MA, Seed JL, Kensler TW . An overview of the relationship between oxidative stress and chemical carcinogenesis Free Radical Biol Med 1991 10: 201–209
Williams JA, Stone EM, Millar BC, Hewer A, Phillips DH . Pathways of heterocyclic amine activation in the breast: DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) formed by peroxidases and in human mammary epithelial cells and fibroblasts Mutagenesis 2000 15: 149–154
Yamalik N, Caglayan F, Kilinc K, Kilinc A, Tumer C . The importance of data presentation regarding gingival crevicular fluid myeloperoxidase and elastase-like activity in periodontal disease and health status J Periodontol 2000 71: 460–467
Austin GE, Lam L, Zaki SR et al. Sequence comparison of putative regulatory DNA of the 5′ flanking region of the myeloperoxidase gene in normal and leukemic bone marrow cells Leukemia 1993 7: 1445–1450
Piedrafita FJ, Molander RB, Vansant G, Orlova EA, Pfahl M, Reynolds WF . An Alu element in the myeloperoxidase promoter contains a composite SP1- thyroid hormone-retinoic acid response element J Biol Chem 1996 271: 14412–14420
Cascorbi I, Henning S, Brockmöller J et al. Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant–463A of the myeloperoxidase gene Cancer Res 2000 60: 644–649
London SJ, Lehman TA, Taylor JA . Myeloperoxidase genetic polymorphism and lung cancer risk Cancer Res 1997 57: 5001–5003
Schabath MB, Spitz MR, Zhang X, Delclos GL, Wu X . Genetic variants of myeloperoxidase and lung cancer risk Carcinogenesis 2000 21: 1163–1166
Matsuo K, Hamajima N, Shinoda M et al. Possible risk reduction in esophageal cancer associated with MPO −463 A allele J Epidemiol 2001 11: 109–114
Nikpoor B, Turecki G, Fournier C, Theroux P, Rouleau GA . Myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians Am Heart J 2001 142: 336–339
Hamajima N, Matsuo K, Suzuki T et al. Low expression myeloperoxidase genotype negatively associated with Helicobacter pylori infection Jpn J Cancer Res 2001 92: 488–493
Reynolds WF, Rhees J, Maciejewski D et al. Myeloperoxidas polymorphism is associated with gender specific risk for Alzheimer’s disease Exp Neurol 1999 155: 31–41
Nagra RM, Becher B, Tourtellotte WW et al. Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis J Neuroimmunol 1997 78: 97–107
Porter W, Saville B, Hoivik D, Safe S . Functional synergy between the transcription factor SP1 and the estrogen receptor Mol Endocrinol 1997 11: 1569–1580
Reynolds WF, Hiltunen M, Pirskanen M et al. MPO and APOε4 polymorphisms interact to increase risk for AD in Finnish males Neurology 2000 55: 1284–1290
Yamada M, Yoshida M, Hashinaka K . Identification of transcriptional cis-elements in introns 7 and 9 of the myeloperoxidase gene J Biol Chem 1993 268: 13479–13485
Jansson G . Oestrogen-induced enhancement of myeloperoxidase activity in human polymorphonuclear leukocytes–a possible cause of oxidative stress in inflammatory cells Free Radical Res Commun 1991 14: 195–208
Marcozzi FG, Madia F, DelBianco G, Mattei E, deFeo G . Lacrimal fluid peroxidase activity during the menstrual cycle Curr Eye Res 2000 20: 178–182
Bekesi G, Kakucs R, Varbiro S et al. Induced myeloperoxidase activity and related superoxide inhibition during hormone replacement therapy Br J Obstet Gynaecol 2001 108: 474–481
Santanam N, Shern-Brewer R, McClatchey R et al. Estradiol as an antioxidant: incompatible with its physiological concentrations and function J Lipid Res 1998 39: 2111–2118
Klinger G, Glanzer S, Sigusch B, Klinger G, Romer W . Influence of sexual steroids on cell functions of PMNL in the gingival sulcus Pharmazie 2000 55: 678–680
Genco RJ . Current view of risk factors for periodontal disease J Periodontol 1996 67: 1041–1049
John U, Greiner B, Hensel E et al. Study of Health in Pomerania (SHIP) – A health examination survey in an east German region: Objectives and design Soz Praventivmed 2001 46: 186–194
Caraballo RS, Giovino GA, Pechacek TF, Mowery PD . Factors associated with discrepancies between self-reports on cigarette smoking and measured serum cotinine levels among persons aged 17 years or older: Third National Health and Nutrition Examination Survey, 1988–1994 Am J Epidemiol 2001 153: 807–814
Botto LD, Khoury MJ . Commentary: facing the challenge of gene-environment interaction: the two-by-four table and beyond Am J Epidemiol 2001 153: 1016–1020
Acknowledgements
We wish to thank Mrs Ingrid Geissler for her skilful technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work is part of the Community Medicine Research net (CMR) of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grant no. ZZ9603), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. The CMR gathers several research projects which share data from the population-based Study of Health in Pomerania. (SHIP; http://www.medizin.uni-greifswald.de/cm).
Rights and permissions
About this article
Cite this article
Meisel, P., Krause, T., Cascorbi, I. et al. Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles. Genes Immun 3, 102–106 (2002). https://doi.org/10.1038/sj.gene.6363840
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363840
Keywords
This article is cited by
-
S100, bcl2 and myeloperoxid protein expirations during periodontal inflammation
BMC Oral Health (2015)
-
Impact of Genetic Polymorphisms on the Smoking-related Risk of Periodontal Disease: the Population-based Study SHIP
Tobacco Induced Diseases (2003)
-
Looking back and looking forward
Genes & Immunity (2003)