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

Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a multifactorial disorder with significant genetic influence. Recently, evide nce of linkage on chromosome 7q near the intestinal mucin gene MUC3 was rep orted by an affected sib-pair analysis. Previous reports indicate a possibl e mucin abnormality in UC patients, but whether genetic differences in a sp ecific mucin gene are associated with UC is unknown. Here we analysed polym orphisms of variable number of tandem repeats (VNTRs) within this gene usin g DNAs obtained from 243 Japanese (75 patients with UC and 168 controls), a nd to confirm the result we undertook a two-stage examination using 328 Cau casian samples (72 and 85 with UC in the first and second stages, respectiv ely, and 171 controls). When the frequency of patients carrying one or two rare VNTR alleles was compared with that of controls, a significant increas e 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 seco nd 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 r are alleles of the MUGS gene may confer genetic predisposition to UC.