Human Molecular Genetics, Vol 8, 307-311, Copyright © 1999 by Oxford University Press
K Kyo, M Parkes, Y Takei, H Nishimori, P Vyas, J Satsangi, J Simmons, H Nagawa, S Baba, D Jewell, T Muto, GM Lathrop and Y Nakamura
Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a
multifactorial disorder with significant genetic influence. Recently,
evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3
was reported by an affected sib-pair analysis. Previous reports indicate a
possible mucin abnormality in UC patients, but whether genetic differences
in a specific mucin gene are associated with UC is unknown. Here we
analysed polymorphisms of variable number of tandem repeats (VNTRs) within
this gene using DNAs obtained from 243 Japanese (75 patients with UC and
168 controls), and to confirm the result we undertook a two-stage
examination using 328 Caucasian samples (72 and 85 with UC in the first and
second stages, respectively, and 171 controls). When the frequency of
patients carrying one or two rare VNTR alleles was compared with that of
controls, a significant increase was found first in Japanese patients (odds
ratio 2.72, 95% CI 1.17- 6.32, P = 0. 0308). In Caucasians, the odds ratio
was 2.80 (95% CI 1.36- 5.75, P = 0.0079) in the first stage, 2.43 (95% CI
1.20-4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P =
0.0024) in total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P =
0.0001). This result suggests that rare alleles of the MUC3 gene may confer
genetic predisposition to UC.
ARTICLES
Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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