© 2004 Blackwell Publishing Ltd, European Journal of Immunogenetics 31, 11–14 11 Blackwell Publishing, Ltd. Analysis of the CC chemokine receptor 5 (CCR5) ∆32 polymorphism in Behçet’s disease X. Yang,* T. Ahmad,* F. Gogus,† G. R. Wallace,‡ W. Madanat,§ C. A. Kanawati,¶ M. R. Stanford,‡ F. Fortune,** D. P. Jewell* & S. E. Marshall†† Summary Chemokines are important determinants of the early inflammatory response. The CC chemokine receptor 5 (CCR5) ∆32 variant results in a non-functional form of the chemokine receptor, and has been implicated in a variety of immune-mediated diseases. To investigate its role in the pathogenesis of Behçet’s disease, we studied 350 patients and 519 healthy controls from three ethnic groups. While significant inter-ethnic variation in allele frequency was observed, no association was identified with disease, even when data were stratified by the known susceptibility gene HLA-B*51. Introduction Behçet’s disease (Behçet’s disease, online mendelian inheritance in man (OMIM) 109650) is a chronic, multisystemic, inflammatory vasculitis characterized by recurrent oral and genital ulceration, uveitis and skin lesions (Sakane et al., 1999). In addition, it frequently involves the skin, joints, central nervous system, and gastrointestinal tract. The aetiology of Behçet’s disease remains unknown, but the triggering of a profound inflammatory response by an undefined environmental factor in a genetically susceptible host remains the most widely held hypothesis (Direskeneli, 2001). Behçet’s disease is common along the Silk Road, an ancient trading route between the Mediterranean and East Asia, where it is an important cause of morbidity. Turkey has the highest prevalence of disease (80–370 cases per 100 000 population; Sakane et al., 1999; Idil et al., 2002); in contrast, the annual incidence in the UK is only 1–2 per 100 000 (Sakane et al., 1999). Susceptibil- ity to Behçet’s disease has consistently been associated with variants in the HLA complex, particularly HLA- B*51 (Verity et al., 1999a). However, the relative risk of disease associated with HLA-B*51 varies widely in different ethnic populations, indicating that other genetic or environmental factors must also be involved. Chemokines are low-molecular-weight proteins that play a major role in the inflammatory response by activat- ing cellular chemotaxis. Peripheral blood leukocytes express a variety of different chemokine receptors. CC chemokine receptor 5 (CCR5) is a key determinant of lymphocyte trafficking which mediates the activation of cells by the proinflammatory chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β and regulated upon activation, normal T cell expressed and secreted cytokine (RANTES). In addition, CCR5 serves as a cofactor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1) (Deng et al., 1996; Dragic et al., 1996). This has been the subject of extensive interest, as a 32-bp deletion of the CCR5 gene (CCR5 ∆32) results in the expression of a truncated, non-functional receptor. This variant confers significant protection from HIV infection and progression (reviewed in O’Brien & Moore, 2000), and recent studies have also demonstrated associ- ations with a range of immunological diseases (Godessart & Kunkel, 2001) including rheumatoid arthritis (Zapico et al., 2000), multiple sclerosis (Schreiber et al., 2002), and outcome after renal transplantation (Fischereder et al., 2001). Active Behçet’s disease is associated with increased activity of a variety of different chemokines: elevated serum or whole blood levels of interleukin (IL)-8, growth related oncogene (GRO)α, macrophage/ monocyte chemotactic protein (MCP)-1α, MIP-1β and RANTES have been associated with Behçet’s disease (al-Dalaan et al., 1995; Verma et al., 1997; Katsantonis et al., 2000; Zouboulis et al., 2000; Bozkurt et al., 2003; Kaburaki et al., 2003). Furthermore, both CXC and CC chemokines are increased in the aqueous humour of * Gastroenterology Unit, University of Oxford, Oxford, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK, † Department of Rheumatology, Cerrahpasa Medical Faculty, Istanbul, Turkey, ‡ Department of Ophthalmology, St Thomas Hospital, London, UK, § The Jordan Hospital, Amman, Jordan, ¶ St John Ophthalmic Hospital, East Jerusalem, Israel, ** Centre for Clinical and Diagnostic Sciences, St Barthlomew and the Royal London School of Medicine and Dentistry, London, UK, and †† Department of Immunology, Wright- Fleming Institute, Imperial College, London, UK. Received 2 October 2003; revised 30 December 2003; accepted 16 January 2004 Correspondence: Tariq Ahmad, Gastroenterology Unit, University of Oxford, Oxford, Gibson Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. E-mail: tariq.ahmad@ndm.ox.ac.uk