Impact of Genetic Polymorphisms on the Smoking-related Risk of Periodontal Disease: the Population-based Study SHIP
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Department of Pharmacology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Department of Immunology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Department of Anatomy, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Department of Epidemiology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Department of Periodontics, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Publication date: 2003-09-15
Corresponding author
P Meisel   

Department of Pharmacology, F.-Loeffler.Str.23d, D-17487 Greifswald, Germany
Tobacco Induced Diseases 2003;1(September):197
Periodontitis is a bacterial inflammatory disease leading to attachment loss with the consequence of tooth loss. There exists a multifactorial risk pattern including bacterial challenge, smoking, age, sex, diabetes, socio-economic and genetic factors. Smoking has the highest impact on the course of the disease modulated by all the other factors. Here, we report the relationship between smoking and the polymorphisms of genetic polymorphisms inflicted in the pathogenesis. In a randomly selected population-based study, 1083 subjects were typed for the polymorphisms of the IL-1 genotype, FcγRIIIb receptor gene, myeloperoxidase and Nacetyltransferase (NAT2) and related to their periodontal state. Smoking behavior was assessed including present and past quality and quantity of smoking. There is a significant dose-effect relationship between the exposure to tobacco smoke and the extent of periodontal disease assessed as attachment loss and tooth loss. Moreover, there are gene-environmental interactions as subjects bearing variant genotypes show an enhanced smoking-associated risk of the disease modulated by these genotypes. In nonsmokers, the impact of these genetic polymorphisms is mostly negligible. This study provides support for the hypothesis that subjects bearing genetic variants of polymorphically expressed phenotypes are at an increased risk of periodontitis when smoking. Mostly, this may be accomplished via the influence of smoking-related impairment on defense mechanisms rather than on the pathogenic pathways.
Hugoson A, Norderyd O, Slotte C, Thorstensson H: Distribution of periodontal disease in a Swedish adult population 1983 and 1993. Journal of Clinical Periodontology. 1973, 25: 542-548. 10.1111/j.1600-051X.1998.tb02485.x.
Albandar JM, Brunelle JA, Kingman A: Destructive periodontal disease in adults 30 years of age and older in the United States, 1988–1994. Journal of Periodontology. 1999, 70: 13-29. 10.1902/jop.1999.70.1.13.
Beck JD: Risk revisited. Community Dentistry and Oral Epidemiology. 1998, 26: 220-225. 10.1111/j.1600-0528.1998.tb01954.x.
Beck JD, Slade GD: Epidemiology of periodontal diseases. Current Opinion in Periodontology. 1996, 3: 3-9.
Landi L, Amar S, Polins AS, Van Dyke TE: Host mechanisms in the pathogenesis of periodontal disease. Current Opinion in Periodontology. 1997, 4: 3-10.
Michalowicz BS, Diehl SR, Gunsolley JC, Sparks BS, Brooks CN, Koertge TE, Califano JV, Burmeister JA, Schenkein HA: Evidence of a substantial genetic basis for risk of adult periodontitis. Journal of Periodontology. 2000, 71: 1699-1707. 10.1902/jop.2000.71.11.1699.
Hart TC, Kornman KS: Genetic factors in the pathogenesis of periodontitis. Periodontology. 2000, 14: 202-215. 10.1111/j.1600-0757.1997.tb00198.x. –1997.
Burgan SW: The role of tobacco use in periodontal diseases: a literature review. General Dentistry. 1997, 45: 449-460.
Kinane DF, Chestnutt IG: Smoking and periodontal disease. Critical Reviews in Oral Biology and Medecine. 2000, 11: 356-365. 10.1177/10454411000110030501.
Gelskey SC: Cigarette smoking and periodontitis: methodology to assess the strength of evidence in support of a causal association. Community Dentistry and Oral Epidemiology. 1999, 27: 16-24. 10.1111/j.1600-0528.1999.tb01987.x.
Meisel P, Carlsson LE, Sawaf H, Fanghaenel J, Greinacher A, Kocher T: Polymorphisms of Fcγ-receptors RIIa, RIIIa, and RIIIb in patients with adult periodontal diseases. Genes and Immunity. 2001, 2: 258-262. 10.1038/sj.gene.6363777.
Kobayashi T, Pol van der WL, Winkel van de JG, Hara K, Sugita N, Westerdaal NA, Yoshie H, Horigome T: Relevance of IgG receptor IIIb (CD16) polymorphism to handling of Porphyromonas gingivalis: implications for the pathogenesis of adult periodontitis. Journal of Periodontal Research. 2000, 35: 65-73. 10.1034/j.1600-0765.2000.035002065.x.
Meisel P, Krause T, Cascorbi I, Schroeder W, Herrmann F, John U, Kocher T: Gender and smoking-related risk reduction of periodontal disease with variant myelo-peroxidase alleles. Genes and Immunity. 2002, 3: 102-106. 10.1038/sj.gene.6363840.
Kocher T, Sawaf H, Fanghaenel J, Timm R, Meisel P: Association between bone loss in periodontal disease and polymorphism of N-acetyltransferase (NAT2). Journal of Clinical Periodontology. 2002, 29: 21-27. 10.1034/j.1600-051x.2002.290104.x.
Kornman KS, di Giovine FS: Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis. Annals of Periodontology. 1998, 3: 327-338.
Meisel P, Siegemund A, Grimm R, Herrmann F, John U, Schwahn C, Kocher T: The interleukin-1 polymorphism, smoking, and the risk of periodontal disease in the population-based SHIP study. Journal of Dental Research. 2003, 82: 189-193. 10.1177/154405910308200308.
Chang YC, Yang SF, Lai CC, Liu JY, Hsieh YS: Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal pathogens in human periodontal ligament fibroblast cultures. Journal of Periodontal Research. 2002, 37: 196-203. 10.1034/j.1600-0765.2002.00663.x.
Hensel E, Gesch D, Biffar R, Bernhardt O, Kocher T, Splieth C, Born G, John U: Study of health in Pomerania (SHIP), a health survey in an east German region. Objectives and design of the oral health section. Quintessence International. 2003, 34 (34): 370-378.
Caraballo RS, Giovino GA, Pechacek TF, Mowery PD: Factors associated with discrepancies between self-reports on cigarette smoking and measured serum cotinin levels among persons aged 17 years or older. American Journal of Epidemiology. 2001, 153: 807-814. 10.1093/aje/153.8.807.
Kornman KS, Crane A, Wang HY, di Giovine FS, Newman MG, Pirk FW, Wilson TG, Higginbottom FL, Duff GW: The interleukin-1 genotype as a severity factor in adult periodontal disease. Journal of Clinical Periodontology. 1997, 24: 72-77. 10.1111/j.1600-051X.1997.tb01187.x.
McDowell TL, Symons JA, Ploski R, Forre O, Duff GW: A genetic association between juvenile rheumatoid arthritis and novel interleukin 1α polymorphism. Arthritis and Rheumatism. 1995, 38: 221-228. 10.1002/art.1780380210.
Cascorbi I, Henning S, Brockmöller J, Gephart J, Meisel C, Muller JM, Loddenkemper R, Roots I: Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant – 463A of the myeloperoxidase gene. Cancer Research. 2000, 60: 644-649.
Meisel P, Timm R, Sawaf H, Fanghaenel J, Siegmund W, Kocher T: Polymorphism of the N-acetyltransferase (NAT2), smoking and the potential risk of periodontal disease. Archives of Toxicology. 2000, 74: 343-348. 10.1007/s002040000136.
Weber WW: Pharmacogenetics. 1997, New York, Oxford, Oxford University Press, 190.
Koene HR, Kleijer M, Algra J, Roos D, Borne von dem AEG, de Haas M: FcγRIIIa-158 V/F polymorphism influences the binding of IgG by NK cell FcγRIIIa, indepently of the FcγRIIIa-48L/R/H phenotype. Blood. 1997, 90: 1109-1114.
DeHaas M, Kleijer M, van Zwieten R, Roos D, Borne von dem AE: Neutrophil Fc gamma RIIIb deficiency, nature, and clinical consequences: a study of 21 individuals from 14 families. Blood. 1995, 86: 2403-2413.
Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, Tew JG: Tobacco and smoking: environmental factors that modify the host response (immune system) and have an impact on periodontal health. Critical Reviews in Oral Biololgy and Medicine. 1997, 8: 437-460. 10.1177/10454411970080040501.
Ottman R: Gene-environment interaction and public health. American Journal of Human Genetics. 1995, 56: 821-823.
Quinn SM, Zhang JB, Gunsolley JC, Schenkein JG, Schenkein HA, Tew JG: Influence of smoking and race on immunoglobulin G subclass concentrations in early-onset periodontitis patients. Infection and Immunity. 1996, 64: 2500-2505.
Lee M, Kirlin W, Sturrup M, Rodriguez J, Urso P: Variation in the response of T cells to concanavalin A after in vitro exposure to benz(a)pyrene and 2-aminofluorene. Immunopharmacology and Immunotoxicology. 1996, 18: 309-321. 10.3109/08923979609052738.
Sulica A, Metes D, Gherman M, Whiteside TL, Herberman RB: Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro. European Journal of Immunology. 1996, 26: 1199-1203. 10.1002/eji.1830260602.
Fredriksson M, Bergström K, Åsman B: IL-8 and TNF-α from peripheral neutrophils and acute-phase proteins in periodontitis. Journal of Clinical Periodontology. 2002, 29: 123-128. 10.1034/j.1600-051x.2002.290206.x.
Engebretson SP, Lamster IB, Herrera-Abreu M, Celenti RS, Timms JM, Chaudhary AG, di Giovine FS, Kornman KS: The influence of interleukin gene polymorphism on expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissue and gingival crevicular fluid. Journal of Periodontology. 1999, 70: 567-573. 10.1902/jop.1999.70.6.567.
Wendell KJ, Stein SH: Regulation of cytokine production in human gingival fibroblasts following tretament with nicotine and lipopolysaccharides. Journal of Periodontology. 2001, 72: 1038-1044. 10.1902/jop.2001.72.8.1038.
Zeidel A, Beilin B, Yardeni I, Mayburd E, Smirnov G, Bessler H: Immune response in asymptomatic smokers. Acta Anaesthesiologica Scandinavica. 2002, 46: 959-964. 10.1034/j.1399-6576.2002.460806.x.
Berger P, McConnell JP, Nunn M, Kornman KS, Sorrell J, Stephenson K, Duff GW: C-reactive protein levels are influenced by common IL-1 gene variations. Cytokine. 2002, 17: 171-174. 10.1006/cyto.2001.0974.
Ouyang Y, Virasch N, Hao P, Aubrey MT, Mukerjee N, Bierer BE, Freed BM: Suppression of human IL-1beta, IL-2, IFN-gamma, and TNF-alpha production by cigarette smoke extracts. Journal of Allergy and Clinical Immunology. 2000, 106: 280-287. 10.1067/mai.2000.107751.
Bostrom L, Linder LE, Bergstrom J: Smoking and GCF levels of IL-1beta and IL-1ra in periodontal disease. Journal of Clinical Periodontology. 2000, 27: 250-255. 10.1034/j.1600-051x.2000.027004250.x.
Uetrecht JP: Myeloperoxidase as a generator of drug free radicals. Biochemical Society Symposium. 1995, 61: 163-170.
Hlavica P, Golly I, Lehnerer M, Schulze J: Primary aromatic amines: their N-oxidative bioactivation. Human & Experimental Toxicology. 1997, 16: 441-448. 10.1177/096032719701600805.
Buchmann R, Hasilik A, Van Dyke TE, Lange DE: Amplified crevicular leukocyte activity in aggressive periodontal disease. Journal of Dental Research. 2002, 81: 716-721. 10.1177/154405910208101012.
Soder B, Jin LJ, Wickholm S: Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis. Journal of Clinical Periodontology. 2002, 29: 384-391. 10.1034/j.1600-051X.2002.290502.x.
Meisel P, Schwahn C, Gesch D, Bernhardt O, John U, Kocher T: Dose-effect relation of smoking and the interleukin-1 (IL-1) gene polymorphism in periodontal disease. Journal of Periodontology. 2003.
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