期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 79, 期 3, 页码 439-448出版社
CELL PRESS
DOI: 10.1086/505915
关键词
-
资金
- NIAID NIH HHS [R01 AI032738, R37 AI032738, AI32738] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI032738] Funding Source: NIH RePORTER
Defensins are endogenous antimicrobial peptides that protect the intestinal mucosa against bacterial invasion. It has been suggested that deficient defensin expression may underlie the chronic inflammation of Crohn disease ( CD). The DNA copy number of the beta-defensin gene cluster on chromosome 8p23.1 is highly polymorphic within the healthy population, which suggests that the defective beta-defensin induction in colonic CD could be due to low beta-defensin gene copy number. Here, we tested this hypothesis, using genomewide DNA copy number profiling by array-based comparative genomic hybridization and quantitative polymerase-chain-reaction analysis of the human beta-defensin 2 (HBD-2) gene. We showed that healthy individuals, as well as patients with ulcerative colitis, have a median of 4 ( range 2 - 10) HBD-2 gene copies per genome. In a surgical cohort with ileal or colonic CD and in a second large cohort with inflammatory bowel diseases, those with ileal resections/disease exhibited a normal median HBD-2 copy number of 4, whereas those with colonic CD had a median of only 3 copies per genome ( for the surgical cohort; P = .008 P = .032 for the second cohort). Overall, the copy number distribution in colonic CD was shifted to lower numbers compared with controls ( for both the surgical cohort and the cohort with inflammatory bowel diseases). Individuals with P = .002 <= 3 copies have a significantly higher risk of developing colonic CD than did individuals with >= 4 copies ( odds ratio 3.06; 95% confidence interval 1.46 - 6.45). An HBD-2 gene copy number of < 4 was associated with diminished mucosal HBD-2 mRNA expression (P = 0.033). In conclusion, a lower HBD-2 gene copy number in the beta-defensin locus predisposes to colonic CD, most likely through diminished beta-defensin expression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据