AN ASSOCIATION STUDY WITH BEHCET DISEASE USING NEW MICROSATELLITE MARKERS
WITHIN THE HLA CLASS I REGION.
M Ota 1, Y Katsuyama2,
N Mizuki3, H Ando4 , G Tamiya5, A Oka5,
T Shina 5, S Ohno3, H Inoko5, Dept. of
Legal Med.1 and Dept. of Pharmacy 2, Shinshu Univ.
School of Med., Nagano, Dept. of Ophthalmology, Yokohama City Univ. School
of Med.3, Japanese Red Cross, Kanagawa Shonan Blood Center4,
Dept. of Genetic Information, Division of Molecular Life Science5,
Tokai Univ. School of Med., Kanagawa.
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Behcet disease is associated with HLA-B51 which is one
of the relatively frequent antigens in many different ethnic groups including
Asian and Eurasian populations. However, it is uncertain whether HLA-B51
itself or a closely linked gene is responsible for developing Behcet disease.
We performed an association study using new microsatellite markers we had
found in the course of large scale genome sequencing of the HLA-class I
region in order to precisely map a pathogenetic gene involved in the development
of Behcet disease. Methods: Seventy-four Japanese patients with Behcet
disease, and 132 unrelated and sex-matched Japanese healthy controls were
enrolled in this study. Eight different microsatellite markers dispersed
around the HLA-B locus were selected to detect repeat polymorphism using
an automated DNA sequencer after PCR amplification. Results: Some
alleles in every loci showed statistically significant association with
the disease by the chi-square method with the continuity correction and
Fishers' exact probability test. The allele frequencies of four markers
in close proximity to the HLA-B gene were significantly deviated from Hardy-Weinberg
equilibrium in the disease group. Furthermore, genotypic distributions
computed by the Mrkov chain method were significantly differentiated in
five loci spanning the 150kb segment from the MICA, HLA-B, HLA-C genes
between the disease and control groups. These results suggest that the
pathogenetic gene for developing Behcet disease is narrowed down within
the 150kb around the HLA-B locus.