Polymorphisms in the 5 0 flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population Takeuchi-Hatanaka K, Ohyama H, Nishimura F, Kato-Kogoe N, Soga Y, Matsushita S, Nakasho K, Yamanegi K, Yamada N, Terada N, Takashiba S. Polymorphisms in the 5 0 flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population. J Clin Periodontol 2008; 35: 317–323. doi: 10.1111/j.1600-051X. 2008.01208.x. Abstract Objectives: The expression of interleukin (IL)-12Rb2 molecule is a crucial regulatory factor in the T-helper type (Th) 1 differentiation of T cells. To elucidate the role of the cell-mediated immune (CMI) response in the pathogenesis of periodontitis, Japanese periodontal patients were subjected to single nucleotide polymorphism (SNP) analyses of the 5 0 flanking region of IL12RB2, whose variants are frequently detected in lepromatous leprosy patients, in which the very weak cellular immune response is caused by low expression of IL-12Rb2. Material and Methods: The gene polymorphisms of the 5 0 flanking region of IL12RB2 were examined in subjects with several types of periodontal disease and in healthy controls. Serum immunoglobulin (Ig) G antibody titres against periodontopathic bacteria were measured and compared in periodontal patients with and without variant alleles of IL12RB2. Results: The frequencies of variant alleles of IL12RB2 were significantly higher in aggressive periodontitis patients as compared with healthy controls or chronic periodontitis patients. Serum IgG titres against all periodontal bacteria examined in subjects carrying variant alleles were higher than those in subjects without variant alleles. Conclusion: IL-12Rb2 SNPs could be useful as genetic markers to access the susceptibility of the general population to periodontal disease. Low CMI responses or high humoral responses are associated with the pathogenesis of inflammatory periodontal diseases. Key words: CMI responses; IgG; IL12RB2; periodontitis; SNPs Accepted for publication 14 January 2008 Periodontitis is an infectious disease initially caused by the infection of the dental plaque (biofilm) with anaerobic, Gram-negative bacteria. In the lesions, host defence functions against these microorganisms are evoked by recruit- ing many kinds of immunoregulatory cells. In such immune systems, it has been postulated that cytokines produced by CD4 1 T-helper (Th) cells play an important role in host defense against Kazu Takeuchi-Hatanaka 1,n , Hideki Ohyama 2,n , Fusanori Nishimura 3 , Nahoko Kato-Kogoe 2 , Yoshihiko Soga 1,4 , Sho Matsushita 5 , Keiji Nakasho 2 , Koji Yamanegi 2 , Naoko Yamada 2 , Nobuyuki Terada 2 and Shogo Takashiba 1 1 Department of Pathophysiology/Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2 Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan; 3 Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan; 4 National Sanatorium Oku-Komyo-En, Setouchi, Japan; 5 Department of Allergy and Immunology, Saitama Medical University, Moroyama, Japan Conflict of interest and source of funding statement The authors declare that they have no con- flict of interests This study was supported, in part, by a Grant-in-Aid for Researchers, Hyogo College of Medicine, and a Grant-in-Aid for Scientific Research (A) (No. 16209062 and No. 18209061) and (C) (No. 18592274 and No. 19592399) from the Japan Society for the Promotion of Science. n These authors contributed equally to this work. J Clin Periodontol 2008; 35: 317–323 doi: 10.1111/j.1600-051X.2008.01208.x 317 r 2008 The Authors. Journal compilation r 2008 Blackwell Munksgaard