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 amultifactorial disorder with significant genetic influence. Recently,evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3was reported by an affected sib-pair analysis. Previous reports indicate apossible mucin abnormality in UC patients, but whether genetic differencesin a specific mucin gene are associated with UC is unknown. Here weanalysed polymorphisms of variable number of tandem repeats (VNTRs) withinthis gene using DNAs obtained from 243 Japanese (75 patients with UC and168 controls), and to confirm the result we undertook a two-stageexamination using 328 Caucasian samples (72 and 85 with UC in the first andsecond stages, respectively, and 171 controls). When the frequency ofpatients carrying one or two rare VNTR alleles was compared with that ofcontrols, a significant increase was found first in Japanese patients (oddsratio 2.72, 95% CI 1.17- 6.32, P = 0. 0308). In Caucasians, the odds ratiowas 2.80 (95% CI 1.36- 5.75, P = 0.0079) in the first stage, 2.43 (95% CI1.20-4.92, 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 confergenetic predisposition to UC.