IL-1 cluster gene polymorphisms in Turkish patients with Behc ¸et’s disease A. A. O ¨ zc ¸imen*, K. Dilek†, U ¨ . Bingo ¨l‡, H. Sarıcaog ˘ lu§, A. Sarando ¨l–,O ¨ . Tas ¸ kapılıog ˘ lu**, M. Yurtkuran‡, M. A. Yurtkuran† & H. B. Oral†† Summary Several cytokine genes may play crucial roles in host susceptibility to Behc ¸et’s Disease (BD), since the cyto- kine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL-1 cluster gene polymorphisms with the development of BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD, and 77 healthy control subjects. All genotyping (IL-1a, IL-1b, IL-1R and IL-1Ra) experiments were performed using sequence specific primers PCR (PCR-SSP). When compared to the healthy controls, the frequencies of IL-1Ra IL-1a and IL-1R gene polymorphisms were not significantly different in BD patients. The frequency of IL-1b )511 TT genotype was higher in the BD group in comparison to the control group. Interestingly, we demonstrated that IL-1 b +3962 gene polymorphism seems to be associated with the presence of Erythema nodosum in BD patients. Our data suggest that polymorphisms in IL-1b gene may affect host susceptibility to BD. In order to confirm the biological significance of our results, further studies should be performed in a large-scale study and ⁄ or in different ethnic groups. Introduction Behc ¸et’s disease (BD) is a systemic vasculitis character- ized by inflammatory lesions of urogenital mucosa, eyes, skin, central nervous system and joints. The pathogenesis of BD is not clearly understood and remains to be elucidated. The disease is characterized by infiltration of lymphocytes and neutrophils into the affected organs. It is now well known that cytokines play critical roles in the pathogenesis of BD, because they mediate many of the effector and regulatory func- tions of immune and inflammatory responses (Gul, 2001). Since the previous studies reported that the lev- els of proinflammatory cytokines, including IL-1, TNF-a, IL-6, IL-8, IL-12 and IL18, are increased in the sera of BD patients (Yosipovitch et al., 1995; Hamzaoui et al., 2002; Adam & Calikoglu, 2004; Akdeniz et al., 2004; Ben Ahmed et al., 2004), the interleukin 1 (IL-1) gene cluster has received particular attention as one of the candidate loci for a role in the pathogenesis of BD. IL-1b is a potent proinflammatory cytokine (Dinarello & Wolff, 1993) and IL-1 receptor antagonist (IL-1Ra) is its naturally occurring antago- nist (Dinarello & Thompson, 1991). The genes of IL-1a (IL1A), IL-1b (IL1B), type I IL-1R and IL-1Ra (IL1RN) are located close to each other on chromo- some 2 at band q12–21 and their genomic sequence is well known (Furutani et al., 1986; Webb et al., 1986; Modi et al., 1988; Lafage et al., 1989; Copeland et al., 1991; Lennard et al., 1992; Steinkasserer et al., 1992; Patterson et al., 1993). Additionally, the pro- duction rates of the proinflammatory cytokine IL-1b and anti-inflammatory cytokine IL-1Ra seem to be genetically determined and are associated with genetic markers (Pociot et al., 1992; Danis et al., 1995). There are several reports suggesting that various host genetic factors play significant roles in susceptibil- ity to BD (Pirim et al., 2004; Gunesacar et al., 2007; Bonyadi et al., 2009; Dilek et al., 2009). Therefore, the identification of host genes responsible for sus- ceptibility and resistance to BD should provide a significant contribution for understanding of the path- ogenesis and may lead to the development of new pro- phylaxis and treatment strategies. The in vitro * Department of Biology, Mersin University Faculty of Science and Art, Mersin, Turkiye, † Department of Nephrology & Rheumatology, Uludag University Faculty of Medicine, Bursa, Turkiye, ‡ Department of Physical Medicine & Rehabilitation, Uludag University Faculty Of Medicine, Bursa, Turkiye, § Department of Dermatology, Uludag University Faculty Of Medicine, Bursa, Turkiye, – Department of Psychiatry, Uludag University Faculty of Medicine, Bursa, Turkiye, ** Department of Neurology, Uludag University Faculty Of Medicine, Bursa, Turkiye and †† Immunology Unit, Department of Medical Microbiology, Uludag University Faculty of Medicine, Bursa, Turkiye Received 22 November 2010; revised 18 January 2011; accepted 27 February 2011 Correspondence: Haluk Barbaros Oral, Department of Medical Microbiology, Immunology Unit, Uludag University Faculty of Medi- cine, Bursa, Turkiye. Tel: +90 224 295 4114; Fax: +90 224 442 9181; E-mail: oralb@uludag.edu.tr ª 2011 Blackwell Publishing Ltd, International Journal of Immunogenetics 38, 295–301 295 doi: 10.1111/j.1744-313X.2011.01006.x