Čes. stomatol. Prakt. zub. lék. (Czech Dental Journal) 2015; 115(4): 89-97 | DOI: 10.51479/cspzl.2015.016

Gene Variability in Immunoregulatory Factors in Patients with Chronic Periodontitis and Diabetes Mellitus

P. Bořilová Linhartová1,2,*, S. Valová2, J. Kaštovský1,2, H. Poskerová1, J. Vokurka1, A. Fassmann1, L. Izakovičová Hollá1,2
1 Stomatologická klinika LF MU a FN u sv. Anny, Brno
2 Ústav patologické fyziologie LF MU, Brno

Introduction and aim of study: Genetic predispositions play an important role in the etiopathogenesis of periodontal diseases (CP) and diabetes mellitus (DM). Recent studies have also proven a bidirectional interrelationship between these conditions. The immunoregulatory factors, including signal peptides, so called cytokines, are considered as candidate genes for both of these diseases. The aim of our study was to analyse polymorphisms in selected cytokines, namely in the interleukin-1 (IL-1) gene cluster and IL-6 gene, in patients with CP and with/without DM and compare them with the healthy population.

Methods: 590 subjects were enrolled in this case-control study: 226 healthy/non-periodontitis subjects, 248 patients only with CP, 36 patients with CP and type 1 DM (T1DM), 80 patients with CP and type 2 DM (T2DM). For genotyping methods based on polymerase chain reaction (PCR) and subsequent restriction analysis were used.

Results: The allele and genotype frequencies of the studied polymorphisms, except for a variant in the IL-1B gene, did not differ significantly between the groups of patients and healthy controls. However, in the IL-1 gene cluster, a protective haplotype in CP and risk haplotypes for CP in patients with T2DM or with T1DM were found. In addition, in the IL-6 gene, a significant difference in GGG haplotype frequencies between the groups of patients with CP and healthy controls was identified.

Conclusion: Our results suggest, that contrary to analyses of individual polymorphisms, different haplotypes in the IL-1 gene cluster and IL-6 gene promoter may affect the risk for CP development in patients with/without DM in Czech population. We assume that the determination of haplotypes may have a better predictive value than study of individual allele and genotype frequencies and it should be preferred in genetic analysis of complex diseases.

Keywords: periodontitis; diabetes mellitus; gene variability; cytokines; interleukins

Published: December 1, 2015  Show citation

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Bořilová Linhartová P, Valová S, Kaštovský J, Poskerová H, Vokurka J, Fassmann A, Izakovičová Hollá L. Gene Variability in Immunoregulatory Factors in Patients with Chronic Periodontitis and Diabetes Mellitus. Čes. stomatol. Prakt. zub. lék. 2015;115(4):89-97. doi: 10.51479/cspzl.2015.016.
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    References

    1. Achyut, B. R., Srivastava, A., Bhattacharya, S., Mittal, B.: Genetic association of interleukin 1beta (-511C/T) and interleu-kin-1 receptor antagonist (86 bp repeat) polymorphisms with type 2 diabetes mellitus in North Indians. Clin. Chim. Acta, roč. 377, 2007, č. 1-2, s. 163-169. Go to original source... Go to PubMed...
    2. Armitage, G. C.: Development of a classification system for periodontal diseases and conditions. Ann. Periodontol., roč. 4, 1999, č. 1, s. 1-6. Go to original source... Go to PubMed...
    3. Atieh, M. A., Faggion, C. M., Seymour, G. J.: Cytokines in pa-tients with type 2 diabetes and chronic periodontitis: A systematic review and meta-analysis. Diabetes Res. Clin. Pract., roč. 104, 2014, č. 2, s. 38-45. Go to original source... Go to PubMed...
    4. Bascones-Martínez, A., González-Febles, J., Sanz-Esporrín, J.: Diabetes and periodontal disease. Review of the literature. Am. J. Dent., roč. 27, 2014, č. 2, s. 63-67.
    5. Bid, H. K., Konwar, R., Agrawal, C. G., Banerjee, M.: Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: a study in the north Indian population. Indian J. Med. Sci., roč. 62, 2008, č. 7, s. 259-266. Go to original source... Go to PubMed...
    6. Bulut, U., Develioglu, H., Taner, I. L., Berker, E.: Interleukin-1 beta levels in gingival crevicular fluid in type 2 diabetes mellitus and adult periodontitis. J. Oral Sci., roč. 43, 2001, č. 3, s. 171-177. Go to original source... Go to PubMed...
    7. Češka, R.: Dyslipidémie u osob s diabetem 2. typu a její léčba. Kap. Kardiol., roč. 3, 2011, č. 3, s. 97-101.
    8. Dinarello, C. A.: The IL-1 family and inflammatory diseases. Clin. Exp. Rheumatol., roč. 20, 2002, č. 5, s. 1-13.
    9. Ding, C., Zhao, L., Sun, Y., Li, L., Xu, Y.: Interleukin-1 receptor antagonist polymorphism (rs2234663) and periodontitis susceptibility: a meta-analysis. Arch. Oral Biol., roč. 57, 2012, č. 6, s. 585-593. Go to original source... Go to PubMed...
    10. Erbağci, A. B., Tarakçioğlu, M., Coşkun, Y., Sivasli, E., Sibel Namiduru, E.: Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children. Clin. Biochem., roč. 34, 2001, č. 8, s. 645-650.
    11. Guzman, S., Karima, M., Wang, H. Y., Van Dyke, T. E.: Association between interleukin-1 genotype and periodontal disease in a diabetic population. J. Periodontol., roč. 74, 2003, č. 8, s. 1183-1190. Go to original source... Go to PubMed...
    12. Chan. H. H., Rahim, Z. H., Jessie, K., Hashim, O. H., Taiyeb-Ali, T. B.: Salivary proteins associated with periodontitis in patients with type 2 diabetes mellitus. Int. J. Mol. Sci., roč. 13, 2012, č. 4, s. 4642-4654. Go to original source... Go to PubMed...
    13. Chapple, I. L. C., Genco, R.: Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J. Clin. Periodontol., roč. 40, 2013, Suppl. 14, s. 106-112. Go to original source... Go to PubMed...
    14. Izakovičová Hollá, L., Dvořáková, N., Halaba, T., Znojil, V., Vácha, J., Vaněk, J.: Analýza polymorfismů v genech pro interleukin-1 (IL-1) u českých pacientů s chronickou parodontitidou. Čes. Stomat., roč. 104, 2004, č. 2, s. 48-56.
    15. Izakovičová Hollá, L., Fassmann, A., Stejskalová, A., Znojil, V., Vaněk, J., Vácha, J.: Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis. J. Periodontol., roč. 75, 2004, č. 1, s. 30-36. Go to original source... Go to PubMed...
    16. Izakovičová Hollá, L., Bořilová Linhartová, P., Hrdličková, B., Marek, F., Dolina, J., Řihák, V., Kala. Z.: Haplotypes of the IL-1 gene cluster are associated with gastroesophageal reflux disease and Barrett's esophagus. Hum. Immunol., roč. 74, 2013, č. 9, s. 1161-1169. Go to original source... Go to PubMed...
    17. Jiang, Z. L., Cui, Y. Q., Gao, R., Li, Y., Fu, Z. C., Zhang, B., Guan, C. C.: Study of TNF-α, IL-1β and LPS levels in the gingival crevicular fluid of a rat model of diabetes mellitus and periodontitis. Dis. Markers, roč. 34, 2013, č. 5, s. 295-304. Go to original source...
    18. Kamagata, Y., Miyasaka, N., Inoue, H., Hashimoto, J., Iida, M.: Study of cytokine production in inflamed human gingival tis-sues in periodontitis. Interleukin-1 (IL-1 alpha, beta) and tumor necrosis factor (TNF alpha). Nihon Shishubyo Gakkai Kaishi, roč. 31, 1989, č. 3, s. 843-848. Go to original source... Go to PubMed...
    19. Karimbux, N. Y., Saraiya, V. M., Elangovan, S., Allareddy, V., Kinnunen, T., Kornman, K. S., Duff, G. W.: Interleukin 1 gene polymorphisms and chronic periodontitis in adult whites: a systematic review and meta-analysis. J. Periodontol., roč. 83, 2012, č. 11, s. 1407-1419. Go to original source... Go to PubMed...
    20. Krikovsky, D., Vásárhelyi, B., Treszl, A., Körner, A., Tordai, A., Tulassay, T., Madácsy, L.: Genetic polymorphism of interleukin-1beta is associated with risk of type 1 diabetes mellitus in children. Eur. J. Pediatr., roč. 161, 2002, č. 9, s. 507-508. Go to original source... Go to PubMed...
    21. Kristiansen, O. P., Mandrup-Poulsen, T.: Interleukin-6 and diabetes: the good, the bad, or the indifferent? Diabetes, roč. 54, 2005, s. 114-124. Go to original source...
    22. López, N. J., Venezuela, C. Y., Jara, L.: Interleukin-1 gene cluster polymorphisms associated with periodontal disease in type 2 diabetes. J. Periodontol., roč. 80, 2009, č. 10, s. 1590-1598. Go to original source... Go to PubMed...
    23. Luotola, K., Pääkkönen, R., Alanne, M., Lanki, T., Moilanen, L., Surakka, I., Pietilä, A., Kähönen, M., Nieminen, M. S., Kesäniemi, Y. A., Peters, A., Jula, A., Perola, M., Salomaa, V., Health 2000 AIRGENE Study Groups: Association of variation in the interleukin-1 gene family with diabetes and glucose homeostasis. J. Clin. Endocrinol. Metab., roč. 94, 2009, č. 11, s. 4575-4583. Go to original source... Go to PubMed...
    24. Luotola, K., Pietilä, A., Zeller, T., Moilanen, L., Kähönen, M., Nieminen, M. S., Kesäniemi, Y. A., Blankenberg, S., Jula, A., Perola, M., Salomaa, V., Health 2000 Study, FINRISK97 Study. Association between interleukin-1 (IL-1) gene variations of IL-1 receptor antagonist and the development type 2 diabetes. J. Intern. Med., roč. 269, 2011, č. 3, s. 322-332. Go to original source... Go to PubMed...
    25. Mark, L. L., Haffajee, A. D., Socransky, S. S., Kent, R. L., Guerrero, D., Kornman, K., Newman, M., Stashenko, P.: Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects with adult periodontitis. J. Periodontal Res., roč. 35, 2000, č. 8, s. 172-177. Go to original source... Go to PubMed...
    26. Müller-Steinhardt, M., Ebel, B., Härtel, C.: The impact of interleukin-6 promoter -597/-572/-174 genotype on interleukin-6 production after lipopolysaccharide stimulation. Clin. Exp. Immunol., roč. 147, 2007, č. 2, s. 339-345. Go to original source... Go to PubMed...
    27. Odegaard, J. I., Chawla, A.: Connecting type 1 and type 2 diabetes through innate immunity. Cold Spring Harb. Perspect. Med., roč. 2, 2012, č. 3, a. 007724. doi: 10.1101/cshperspect.a007724. Go to original source... Go to PubMed...
    28. Poskerová, H., Bořilová Linhartová, P., Vokurka, J., Fassmann, A., Izakovičová Hollá, L.: Diabetes a orální zdraví. Čes. Stomat., roč. 114, 2014, č. 5, s. 75-86. Go to original source...
    29. Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E., Ridker, P. M.: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA, roč. 286, 2001, č. 3. s. 327-334. Go to original source... Go to PubMed...
    30. Rafiq, S., Frayling, T. M., Murray, A., Hurst, A., Stevens, K., Weedon, M. N., Henley, W., Ferrucci, L., Bandinelli, S., Corsi, A.-M., Guralnik, J. M., Melzer, D.: A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun., roč. 8, 2007, č. 7, s. 552-559. Go to original source... Go to PubMed...
    31. Rivera-Chavez, F. A., Peters-Hybki, D. L., Barber, R. C., O'Keefe, G. E.: Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses. Shock (Augusta, Ga.), roč. 20, 2003, č. 3, s. 218-223. Go to original source...
    32. Salvi, G. E., Beck, J. D., Offenbacher, S.: PGE2, IL-1 beta, and TNF-alpha responses in diabetics as modifiers of periodontal disease expression. Ann. Periodontol., roč. 3, 1998, č. 1, s. 40-50. Go to original source... Go to PubMed...
    33. Santos Tunes, R., Foss-Freitas, M. C., Nogueira-Filho Gda, R.: Impact of periodontitis on the diabetes-related inflammatory status. J. Can. Dent. Assoc., roč. 76, 2010, s. 35.
    34. Settin, A., Ismail, A., El-Magd, M. A., El-Baz, R., Kazamel, A.: Gene polymorphisms of TNF-alpha-308 (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus. Autoimmunity, roč. 42, 2009, č. 1, s. 50-55. Go to original source... Go to PubMed...
    35. Sharma, N., Joseph, R., Arun, R., Chandni, R., Srinivas, K. L., Banerjee, M.: Cytokine gene polymorphism (interleukin-1β +3954, Interleukin-6 [-597/-174] and tumor necrosis factor-α -308) in chronic periodontitis with and without type 2 diabetes mellitus. Indian J. Dent. Res., roč. 25, 2014, č. 3, s. 375-380. Go to original source... Go to PubMed...
    36. Song, G. G., Choi, S. J., Ji, J. D., Lee, Y. H.: Association between tumor necrosis factor-α promoter -308 A/G, -238 A/G, interleukin-6 -174 G/C and -572 G/C polymorphisms and periodontal disease: a meta-analysis. Mol. Biol. Rep., roč. 40, 2013, č. 8, s. 5191-5203. Go to original source... Go to PubMed...
    37. Steinkasserer. A., Spurr, N. K., Cox, S., Jeggo, P., Sim, R. B.: The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci. Genomics, roč. 13, 1992, č. 3, s. 654-657. Go to original source... Go to PubMed...
    38. Struch, F., Dau, M., Schwahn, C., Biffar, R., Kocher, T., Meisel, P.: Interleukin-1 gene polymorphism, diabetes, and periodontitis: results from the Study of Health in Pomerania (SHIP). J. Periodontol., roč. 79, 2008, č. 3, s. 501-507. Go to original source... Go to PubMed...
    39. Takahashi, K., Takashiba, S., Nagai, A., Takigawa, M., Myoukai, F., Kurihara, H., Murayama, Y.: Assessment of interleukin-6 in the pathogenesis of periodontal disease. J. Periodontol., roč. 65, 1994, č. 2, s. 147-153. Go to original source... Go to PubMed...
    40. Taylor, J. J., Preshaw, P. M., Lalla, E.: A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J. Clin. Periodontol., roč. 40, 2013, Suppl. 14, s. 113-134. Go to original source... Go to PubMed...
    41. Terry, C. F., Loukaci, V., Green, F. R.: Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J. Biol. Chem., roč. 275, 2000, č. 24, s. 18138-18144. Go to original source... Go to PubMed...
    42. Xiao, L. M., Yan, Y. X., Xie, C. J., Fan, W. H., Xuan, D. Y., Wang, C. X., Chen, L., Sun, S. Y., Xie, B.Y., Zhang, J. C.: Association among interleukin-6 gene polymorphism, diabetes and periodontitis in a Chinese population. Oral Dis., roč. 15, 2009, č. 8, s. 547-553. Go to original source... Go to PubMed...

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