Objective. To determine whether differences exist between periodontitis subjects with and without Coronary Heart Disease (CHD) in a Syrian population in the distribution of IL-1 alleles at positions IL-1 +4845, IL-1 +3954, IL-1 ？511, and IL-1RN VNTR. Background. The role of Interleukin-1 genes in the association between periodontitis and CHD has been demonstrated in previous studies. No study has been carried out on the Syrian population to asses for such a role. Methods. 200 Syrian Arab periodontitis patients (184 males, 16 females; mean age 52.61) were divided into two groups: cases group 100 subjects with CHD (92 males, 8 females; mean age 52.06); controls group 100 subjects without CHD (92 males, 8 females; mean age 53.16). Probing depth (PD), clinical attachment loss (CAL), and alveolar bone loss (ABL) were performed for patients. Blood samples were collected for genotyping analysis of IL-1 +4845, IL-1 +3954, and IL-1 ？511 using PCR-RFLP technique and IL-1RN VNTR using normal PCR. Results. An association between both (CAL and ABL) and CHD was shown after adjustment for other confounders (OR: 7.659, ; OR: 3.645, , resp.). Also, an association between allele 2 of IL-1 +4845, IL-1 +3954, and IL-1 ？511 and ABL was shown. Allele 2 of IL-1 +4845 and IL-1 ？511 was associated with ABL among individuals with and without CHD. But after adjustment for other confounders, the association remained only between allele 2 of IL-11 +4845 and both CHD and severe ABL (OR: 0.189, ). Conclusion. Allele 2 of IL-11 +4845 may be considered a risk indicator for having both CHD and severe ABL in the investigated Syrian population. 1. Introduction Periodontitis is a chronic inflammatory disease of multifactorial etiology initiated by specific bacteria that activate host mechanisms which in turn destroy the bone and connective tissues that support the teeth [1]. In recent years, studies have demonstrated that periodontitis is associated with elevated levels of inflammatory cytokines [2], which have a substantial impact on numerous biological activities, and they take part in triggering inflammatory cascades and systems [3]. To illustrate, Interleukin-1 (IL-1) plays a prominent role in the inflammatory response in periodontal lesions. IL-1α and IL-1β upregulate prostaglandin E2 and matrix metalloproteinase and, together with these components, promote the loss of connective tissue and bone in periodontitis lesions [4]. Atherosclerosis is considered the most common cause of Coronary Heart Disease (CHD). It is a variable combination of changes of the intima of arteries that lead
References
[1]
K. S. Kornman, “Mapping the pathogenesis of periodontitis: a new look,” Journal of Periodontology, vol. 79, no. 8, supplement, pp. 1560–1568, 2008.
[2]
P. Hodge and B. Michalowicz, “Genetic predisposition to periodontitis in children and young adults,” Periodontology, vol. 26, no. 1, pp. 113–134, 2001.
[3]
H. Okada and S. Murakami, “Cytokine expression in periodontal health and disease,” Critical Reviews in Oral Biology and Medicine, vol. 9, no. 3, pp. 248–266, 1998.
[4]
C. A. Dinarello, “Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist,” International Reviews of Immunology, vol. 16, no. 5-6, pp. 457–499, 1998.
[5]
R. Ross, “Atherosclerosis: an inflammatory disease,” The New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999.
[6]
G. C. Armitage, “Periodontal infections and cardiovascular disease: how strong is the association?” Oral Diseases, vol. 6, no. 6, pp. 335–350, 2000.
[7]
F. A. Offner, H. Feichtinger, S. Stadlmann et al., “Transforming growth factor-β synthesis by human peritoneal mesothelial cells: induction by interleukin-1,” The American Journal of Pathology, vol. 148, no. 5, pp. 1679–1688, 1996.
[8]
B. S. Bochner, F. W. Luscinskas, M. A. Gimbrone et al., “Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules,” Journal of Experimental Medicine, vol. 173, no. 6, pp. 1553–1556, 1991.
[9]
A. J. Szalai, F. W. Van Ginkel, S. A. Dalrymple, R. Murray, J. R. McGhee, and J. E. Volanakis, “Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice,” Journal of Immunology, vol. 160, no. 11, pp. 5294–5299, 1998.
[10]
S. B. Ng, Y. Tan, and G. R. Guy, “Differential induction of the interleukin-6 gene by tumor necrosis factor and interleukin-1,” Journal of Biological Chemistry, vol. 269, no. 29, pp. 19021–19027, 1994.
[11]
P. J. Haidaris, “Induction of fibrinogen biosynthesis and secretion from cultured pulmonary epithelial cells,” Blood, vol. 89, no. 3, pp. 873–882, 1997.
[12]
L. L. Humphrey, R. Fu, D. I. Buckley, M. Freeman, and M. Helfand, “Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis,” Journal of General Internal Medicine, vol. 23, no. 12, pp. 2079–2086, 2008.
[13]
A. A. Bahekar, S. Singh, S. Saha, J. Molnar, and R. Arora, “The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis,” The American Heart Journal, vol. 154, no. 5, pp. 830–837, 2007.
[14]
W. Al-Tayebb and R. Khattab, Evaluating periodontitis role as a risk factor in atherosclerosis [Ph.D. thesis], Damascus University, Damascus, Syria, 2007.
[15]
K. S. Kornman and G. W. Duff, “Candidate genes as potential links between periodontal and cardiovascular diseases,” Annals of periodontology, vol. 6, no. 1, pp. 48–57, 2001.
[16]
M. C. Herzberg and M. W. Weyer, “Dental plaque, platelets, and cardiovascular diseases,” Annals of periodontology, vol. 3, no. 1, pp. 151–160, 1998.
[17]
D. F. Kinane, “Periodontal diseases' contributions to cardiovascular disease: an overview of potential mechanisms,” Annals of periodontology, vol. 3, no. 1, pp. 142–150, 1998.
[18]
J. D. Beck, S. Offenbacher, R. Williams, P. Gibbs, and R. Garcia, “Periodontitis: a risk factor for coronary heart disease?” Annals of periodontology, vol. 3, no. 1, pp. 127–141, 1998.
[19]
M. J. H. Nicklin, A. Weith, and G. W. Duff, “A physical map of the region encompassing the human interleukin-1α, interleukin-1β, and interleukin-1 receptor antagonist genes,” Genomics, vol. 19, no. 2, pp. 382–384, 1994.
[20]
S. Kenneth Kornman, Allison Crane, Hwa-Ying Wang et al., “The interleukin-1 genotype as a severity factor in adult periodontal disease,” Journal of Clinical Periodontology, vol. 24, no. 1, pp. 72–77, 1997.
[21]
M. L. Laine, M. A. Farré, M. A. Garciagonzález et al., “Polymorphisms of the interleukin-1 gene family, oral microbial pathogens, and smoking in adult periodontitis,” Journal of Dental Research, vol. 80, no. 8, pp. 1695–1699, 2001.
[22]
A. A. Agrawal, A. Kapley, R. K. Yeltiwar, and H. J. Purohit, “Assessment of single nucleotide polymorphism at IL-1A+4845 and IL-1B+3954 as genetic susceptibility test for chronic periodontitis in Maharashtrian ethnicity,” Journal of Periodontology, vol. 77, no. 9, pp. 1515–1521, 2006.
[23]
N. Al-hebshi, A. Shamsan, and M. Al-ak’hali, “Interleukin-1 Two-locus haplotype is strongly associated with severe chronic periodontitis among Yemenis,” Molecular Biology International, vol. 2012, Article ID 231309, 7 pages, 2012.
[24]
N. Karimbux, V. Saraiya, S. Elangovan et al., “Interleukin-1 gene polymorphisms and chronic periodontitis in adult Caucasians: a systematic review and meta-analysis,” Journal of Periodontology, vol. 83, no. 11, pp. 1407–1419, 2012.
[25]
S. E. Francis, N. J. Camp, R. M. Dewberry et al., “Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease,” Circulation, vol. 99, no. 7, pp. 861–866, 1999.
[26]
B. B. Worrall, S. Azhar, P. A. Nyquist, R. H. Ackerman, T. L. Hamm, and T. J. DeGraba, “Interleukin-1 receptor antagonist gene polymorphisms in carotid atherosclerosis,” Stroke, vol. 34, no. 3, pp. 790–793, 2003.
[27]
P. S. Olofsson, Y. Sheikine, K. Jatta et al., “A functional interleukin-1 receptor antagonist polymorphism influences atherosclerosis development: the interleukin-1β: interleukin-1 receptor antagonist balance in atherosclerosis,” Circulation Journal, vol. 73, no. 8, pp. 1531–1536, 2009.
[28]
B. Vicenová, L. Bury？ek, and M. Pospí？ek, “Emerging role of interleukin-1 in cardiovascular diseases,” Physiological Research, vol. 58, no. 4, pp. 481–498, 2009.
[29]
K. S. Kornman, J. Pankow, S. Offenbacher, J. Beck, F. Di Giovine, and G. W. Duff, “Interleukin-1 genotypes and the association between periodontitis and cardiovascular disease,” Journal of Periodontal Research, vol. 34, no. 7, pp. 353–357, 1999.
[30]
Y. Momiyama, R. Hirano, H. Taniguchi, H. Nakamura, and F. Ohsuzu, “Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection,” Journal of the American College of Cardiology, vol. 38, no. 3, pp. 712–717, 2001.
[31]
D. Goteiner, R. Ashmen, N. Lehrman, M. N. Janal, and B. Eskin, “Presence and significance of interleukin-1 polymorphism in patients who present with acute coronary syndrome, angina, and chronic periodontitis: an epidemiologie pilot study,” Journal of Periodontology, vol. 79, no. 1, pp. 138–143, 2008.
[32]
K. Geismar, C. Enevold, L. K. S？rensen et al., “Involvement of interleukin-1 genotypes in the association of coronary heart disease with periodontitis,” Journal of Periodontology, vol. 79, no. 12, pp. 2322–2330, 2008.
[33]
J. M. Stein, R. Smeets, S. Reichert et al., “The role of the composite interleukin-1 genotype in the association between periodontitis and acute myocardial infarction,” Journal of Periodontology, vol. 80, no. 7, pp. 1095–1102, 2009.
[34]
S. T. Sherry, M. H. Ward, M. Kholodov et al., “DbSNP: the NCBI database of genetic variation,” Nucleic Acids Research, vol. 29, no. 1, pp. 308–311, 2001.
[35]
The American Academy of Periodontology, Proceedings of the World Workshop in Clinical Periodontics, The American Academy of Periodontology, Chicago, Ill, USA, 1999.
[36]
P. Newman, F. Carranza, and T. Henri, “Clinical Periodontology,” in Classification of Diseases and Conditions Affecting the Periodontium, Chapter 4, pp. 67–70, 9th edition, 2002.
[37]
J. Haring and L. Howerton, Dental Radiography: Principle and Techniques, chapter 33, 3rd edition, 2000.
[38]
J. K. Tarlow, A. I. F. Blakemore, A. Lennard et al., “Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat,” Human Genetics, vol. 91, no. 4, pp. 403–404, 1993.
[39]
S. Renvert, O. Ohlsson, S. Persson, N. P. Lang, and G. Rutger Persson, “Analysis of periodontal risk profiles in adults with or without a history of myocardial infarction,” Journal of Clinical Periodontology, vol. 31, no. 1, pp. 19–24, 2004.
[40]
J. D. Beck, J. R. Elter, G. Heiss, D. Couper, S. M. Mauriello, and S. Offenbacher, “Relationship of periodontal disease to carotid artery intima-media wall thickness: the Atherosclerosis Risk in Communities (ARIC) study,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 11, pp. 1816–1822, 2001.
[41]
P. Berger, J. P. McConnell, M. Nunn et al., “C-reactive protein levels are influenced by common IL-1 gene variations,” Cytokine, vol. 17, no. 4, pp. 171–174, 2002.
[42]
A. Arman, O. Soylu, A. Yildirim et al., “Interleukin-1 receptor antagonist gene VNTR polymorphism is associated with coronary artery disease,” Arquivos Brasileiros de Cardiologia, vol. 91, no. 5, pp. 268–273, 2008.
[43]
B. Vohnout, A. Di Castelnuovo, R. Trotta et al., “Interleukin-1 gene cluster polymorphisms and risk of coronary artery disease,” Haematologica, vol. 88, no. 1, pp. 54–60, 2003.
[44]
L. Iacoviello, A. Di Castelnuovo, M. Gattone et al., “Polymorphisms of the interleukin-1β gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 1, pp. 222–227, 2005.
[45]
J. Pankow, J. Beck, S. Offenbacher, D. Catallier, and M. Bray, “Association of interleukin-1 gene variants and carotid arterial wall thickness: the ARIC study,” Atherosclerosis, supplement, pp. 1124–1144, 1999.
[46]
S. S. Witkin, S. Gerber, and W. J. Ledger, “Influence of interleukin-1 receptor antagonist gene polymorphism on disease,” Clinical Infectious Diseases, vol. 34, no. 2, pp. 204–209, 2002.
[47]
P. N. Papapanou, A. M. Neiderud, J. Sandros, and G. Dahlén, “Interleukin-1 gene polymorphism and periodontal status: a case-control study,” Journal of Clinical Periodontology, vol. 28, no. 5, pp. 389–396, 2001.
[48]
P. S. G. Prakash and D. J. Victor, “Interleukin-1b gene polymorphism and its association with chronic periodontitis in south Indian population,” International Journal of Genetics and Molecular Biology, vol. 2, no. 8, pp. 179–183, 2010.
[49]
A. Dro？dzik, M. Kurzawski, K. Safronow, and J. Banach, “Polymorphism in interleukin-1beta gene and the risk of periodontitis in a Polish population,” Advances in Medical Sciences, vol. 51, supplement 1, pp. 13–17, 2006.
[50]
S. B. Ferreira, A. P. F. Trombone, C. E. Repeke et al., “An interleukin-1β (IL-1β) single-nucleotide polymorphism at position 3954 and red complex periodontopathogens independently and additively modulate the levels of IL-1β in diseased periodontal tissues,” Infection and Immunity, vol. 76, no. 8, pp. 3725–3734, 2008.
[51]
G. Kaarthikeyan, N. D. Jayakumar, O. Padmalatha, V. Sheeja, M. Sankari, and B. Anandan, “Analysis of the association between interleukin -1β (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population,” Indian Journal of Dental Research, vol. 20, no. 1, pp. 37–40, 2009.
[52]
F. Pociot, J. Molvig, L. Wogensen, H. Worsaae, and J. Nerup, “A TaqI polymorphism in the human interleukin-1β (IL-1β) gene correlates with IL-1β secretion in vitro,” European Journal of Clinical Investigation, vol. 22, no. 6, pp. 396–402, 1992.
[53]
K. Kornman, “Interleukin 1 haplotypes and composite genotypes are associated with increased inflammatory mediators and cardiovascular events,” in Proceedings of the 4th Conference on Cytokines and Inflammation, January 2006.
[54]
S. Shiroddria, J. Smith, I. J. McKay, C. N. Kennett, and F. J. Hughes, “Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1α protein in gingival crevicular fluid of teeth with severe periodontal disease,” Journal of Dental Research, vol. 79, no. 11, pp. 1864–1869, 2000.
[55]
G. C. Armitage, Y. Wu, H. Y. Wang, J. Sorrell, F. S. Di Giovine, and G. W. Duff, “Low prevalence of a periodontitis-associated interleukin-1 composite genotype in individuals of Chinese heritage,” Journal of Periodontology, vol. 71, no. 2, pp. 164–171, 2000.
