COX-2 Is Associated with Periodontitis in Europeans

Abstract

COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were associated with periodontitis in populations of European ethnicity, we genotyped the single-nucleotide polymorphisms (SNPs) rs689466 and rs6681231, the latter a haplotype tagging SNP (htSNP) for rs20417 (r²>0.95), in our large-analysis population of individuals with aggressive (n = 532) and chronic periodontitis (n = 1052), and 2873 healthy control individuals. The rare G allele of htSNP rs6681231 was associated with aggressive periodontitis prior to and after adjustment for the covariates smoking, diabetes, and gender, with an odds ratio of 1.57 (95% confidence interval 1.18–2.08; p = 0.002). The validation of the association of rs20417 by the htSNP rs6681231 provides evidence for a general genetic risk of COX-2 variants in the pathogenesis of periodontitis.

Get full access to this article

View all access options for this article.

References

Barrett JC, Fry B, Maller J, Daly MJ (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265.

Cipollone F, Toniato E, Martinotti S, Fazia M, Iezzi A, Cuccurullo C, et al. (2004). A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. J Am Med Assoc 291:2221–2228.

Coronary Artery Disease Consortium, Samani NJ, Deloukas P, Erdmann J, Hengstenberg C, Kuulasmaa K, McGinnis R, et al. (2009). Large scale association analysis of novel genetic loci for coronary artery disease. Arterioscler Thromb Vasc Biol 29:774–780.

de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D (2005). Efficiency and power in genetic association studies. Nat Genet 37:1217–1223.

Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. (1998). Cyclooxygenase in biology and disease. FASEB J 12:1063–1073.

Elgar G, Vavouri T (2008). Tuning in to the signals: noncoding sequence conservation in vertebrate genomes. Trends Genet 24:344–352.

Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, et al. (2009). Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106:2700–2705.

Ho YP, Lin YC, Yang YH, Ho KY, Wu YM, Tsai CC (2008). Cyclooxygenase-2 Gene-765 single nucleotide polymorphism as a protective factor against periodontitis in Taiwanese. J Clin Periodontol 35:1–8.

Konheim YL, Wolford JK (2003). Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians. Hum Genet 113:377–381.

10.

Laine ML, Farré MA, Crusius JB, van Winkelhoff AJ, Peña AS (2000). The mouthwash: a non-invasive sampling method to study cytokine gene polymorphisms. J Periodontol 71:1315–1318.

11.

Lohinai Z, Stachlewitz R, Szekely AD, Fehér E, Dézsi L, Szabó C (2001). Evidence for the expression of cyclooxygenase-2 enzyme in periodontitis. Life Sci 70:279–290.

12.

Loots GG (2008). Genomic identification of regulatory elements by evolutionary sequence comparison and functional analysis. Adv Genet 61:269–293.

13.

Miyauchi M, Hiraoka M, Oka H, Sato S, Kudo Y, Ogawa I, et al. (2004). Immuno-localization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopolysaccharide. Arch Oral Biol 49:739–746.

14.

Offenbacher S, Odle BM, Van Dyke TE (1986). The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodontal Res 21:101–112.

15.

Offenbacher S, Heasman PA, Collins JG (1993). Modulation of host PGE2 secretion as a determinant of periodontal disease expression. J Periodontol 64(5 Suppl):432S–444S.

16.

Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, et al. (2002). Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 22:1631–1636.

17.

Pollard KS, Salama SR, King B, Kern AD, Dreszer T, Katzman S, et al. (2006). Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2(10):e168.

18.

Schaefer AS, Richter GM, Groessner-Schreiber B, Noack B, Nothnagel M, El Mokhtari NE, et al. (2009). Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis. PLoS Genet 5(2):e1000378.

19.

Schunkert H, Gotz A, Braund P, McGinnis R, Tregouet DA, Mangino M, et al. (2008). Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation 117:1675–1684.

20.

Smith WL, Garavito RM, DeWitt DL (1996). Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160.

21.

Team TRDC (2008). The R Project for Statistical Computing. http://www.r-project.org (link accessed 10/22/09).

22.

Vardar S, Baylas H, Huseyinov A (2003). Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2alpha and clinical parameters of chronic periodontitis. J Periodontol 74:57–63.

23.

Wigginton JE, Cutler DJ, Abecasis GR (2005). A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 76:887–893.

24.

Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, et al. (2008). FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105:13987–13992.

25.

Xie CJ, Xiao LM, Fan WH, Xuan DY, Zhang JC (2009). Common single nucleotide polymorphisms in cyclooxygenase-2 and risk of severe chronic periodontitis in a Chinese population. J Clin Periodontol 36:198–203.

26.

Yen CA, Damoulis PD, Stark PC, Hibberd PL, Singh M, Papas AS (2008). The effect of a selective cyclooxygenase-2 inhibitor (celecoxib) on chronic periodontitis. J Periodontol 79:104–113.

27.

Yucel-Lindberg T, Ahola H, Carlstedt-Duke J, Modéer T (1999). Involvement of tyrosine kinases on cyclooxygenase expression and prostaglandin E2 production in human gingival fibroblasts stimulated with interleukin-1beta and epidermal growth factor. Biochem Biophys Res Commun 257:528–532.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

1.84 MB