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Association of MICA Gene and HLA-B*5101 with Behçet’s Disease in Greece

¹ From the Department of Ophthalmology, Yokohama City University School of Medicine; the ² Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Kanagawa; and the ³ Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan; the ⁴ Department of Hygiene and Epidemiology, University of Athens Medical School; the ⁵ National Tissue Typing Center, George Gennimatas General Hospital, Athens, Greece; and the ⁶ Newton Wellesley Hospital, Department of Internal Medicine, Boston, Massachusetts.

Abstract

PURPOSE. Behçet’s disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations.

METHODS. Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology.

RESULTS. Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023).

CONCLUSIONS. This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.

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