Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3

被引:74
作者
Kyo, K
Parkes, M
Takei, Y
Nishimori, H
Vyas, P
Satsangi, J
Simmons, J
Nagawa, H
Baba, S
Jewell, D
Muto, T
Lathrop, GM
Nakamura, Y
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan
[2] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[3] Hamamatsu Univ Sch Med, Dept Surg 2, Shizuoka 4313192, Japan
[4] Univ Tokyo, Dept Surg 1, Bunkyo Ku, Tokyo 1138655, Japan
[5] Radcliffe Infirm, Dept Gastroenterol, Oxford OX2 6HE, England
关键词
D O I
10.1093/hmg/8.2.307
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 MUGS gene may confer genetic predisposition to UC.
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页码:307 / 311
页数:5
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