DO: 0110894;
Cytogenetic location: 7q22 Genomic coordinates (GRCh38): 7:98,400,001-107,800,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q22 | {Inflammatory bowel disease 11} | 191390 | Multifactorial | 2 |
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, see IBD1 (266600).
Satsangi et al. (1996) performed a genomewide screen for susceptibility genes in inflammatory bowel disease involving 186 affected sib pairs from 160 nuclear families and obtained a lod score of 3.08 on chromosome 7q at marker D7S669.
Using DNA samples from 75 Japanese patients with ulcerative colitis (UC) and 168 controls, Kyo et al. (1999) analyzed variation in the size of the 51-bp repetitive element in the candidate gene MUC3 (158371) on chromosome 7 and found that a significantly greater number of patients carried 1 or 2 rare VNTR alleles compared to controls (odds ratio, 2.72; p = 0.0308). The results were confirmed in a 2-stage study using DNA samples from 157 Caucasian patients with UC and 171 controls (combined OR, 2.60; p = 0.0024). Kyo et al. (1999) concluded that rare alleles of the MUC3 gene may confer genetic predisposition to UC.
Using DNA samples from 30 patients with Crohn disease (CD) and 30 patients with UC, Kyo et al. (2001) identified 11 SNPs and 13 'rare variants' in the 3-prime exonic region of the MUC3A gene. The authors analyzed the 3-prime SNPs in 72 sporadic cases of UC and 70 unrelated patients with CD and found that nonsynonymous SNPs of MUC3A, involving a tyrosine residue with a proposed role in cell signaling, may confer genetic predisposition to CD (p = 0.0132). Kyo et al. (2001) suggested that variants of MUC3A may be involved in the occurrence of UC and CD in distinct manners.
In a genomewide association study involving 1,897,764 SNPs in 1,043 German UC cases and 1,703 controls, Franke et al. (2010) found significant association at SNP rs7809799 on chromosome 7q22, located between the SMURF1 (605568) and KPNA7 (614107) genes (p = 2.68 x 10(-5)). Combined analysis, including 6 replication panels involving a total of 2,539 UC cases and 5,428 controls, yielded a Cochran-Mantel-Haenzsel p = 8.81 x 10(-11) (odds ratio, 1.56; 95% CI 1.36-1.78). Gene ontology analyses for the rs7809799 G allele, which was overrepresented in UC cases, revealed downregulation of IL1F10 (615296), FOXP1 (605515), and BTN3A1 (613593) transcripts.
Franke, A., Balschun, T., Sina, C., Ellinghaus, D., Hasler, R., Mayr, G., Albrecht, M., Wittig, M., Buchert, E., Nikolaus, S., Gieger, C., Wichmann, H. E., and 16 others. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Nature Genet. 42: 292-294, 2010. [PubMed: 20228798] [Full Text: https://doi.org/10.1038/ng.553]
Kyo, K., Muto, T., Nagawa, H., Lathrop, G. M., Nakamura, Y. Associations of distinct variants of the intestinal mucin gene MUC3A with ulcerative colitis and Crohn's disease. J. Hum. Genet. 46: 5-20, 2001. [PubMed: 11289722] [Full Text: https://doi.org/10.1007/s100380170118]
Kyo, K., Parkes, M., Takei, Y., Nishimori, H., Vyas, P., Satsangi, J., Simmons, J., Nagawa, H., Baba, S., Jewell, D., Muto, T., Lathrop, G. M., Nakamura, Y. Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3. Hum. Molec. Genet. 8: 307-311, 1999. [PubMed: 9931338] [Full Text: https://doi.org/10.1093/hmg/8.2.307]
Satsangi, J., Parkes, M., Louis, E., Hashimoto, L., Kato, N., Welsh, K., Terwilliger, J. D., Lathrop, G. M., Bell, J. I., Jewell, D. P. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nature Genet. 14: 199-202, 1996. [PubMed: 8841195] [Full Text: https://doi.org/10.1038/ng1096-199]