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(Investigative Ophthalmology and Visual Science. 2000;41:3702-3708.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Localization of the Pathogenic Gene of Behçet’s Disease by Microsatellite Analysis of Three Different Populations

Nobuhisa Mizuki1,2, Masao Ota3, Kazuro Yabuki1,2, Yoshihiko Katsuyama3, Hitoshi Ando2, Gerassimos D. Palimeris4, Evangelia Kaklamani4, Massimo Accorinti5, Paola Pivetti-Pezzi5, Shigeaki Ohno1 and Hidetoshi Inoko2

1 From the Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 2 Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan; 3 Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan; 4 Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece; and 5 Institute of Ophthalmology, University "La Sapienza," Rome, Italy.

PURPOSE. Behçet’s disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian.

METHODS. The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology.

RESULTS. Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, Pc = 0.000014; Greek, Pc = 0.00047; Italian, Pc = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, Pc = 0.000000000017; Greek, Pc = 0.00000032; Italian, Pc = 0.0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51.

CONCLUSIONS. These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.




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