A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon.

摘要: Defensins are endogenous antimicrobial peptides that protect the intestinal mucosa against bacterial invasion. It has been suggested deficient defensin expression may underlie chronic inflammation of Crohn disease (CD). The DNA copy number beta-defensin gene cluster on chromosome 8p23.1 is highly polymorphic within healthy population, which suggests defective induction in colonic CD could be due to low beta-defensin–gene number. Here, we tested this hypothesis, using genomewide profiling by array-based comparative genomic hybridization and quantitative polymerase-chain-reaction analysis human 2 ( HBD-2 ) gene. We showed individuals, as well patients with ulcerative colitis, have a median 4 (range 2–10) copies per genome. In surgical cohort ileal or second large inflammatory bowel diseases, those resections/disease exhibited normal 4, whereas had only 3 genome P =.008 for cohort; =.032 cohort). Overall, distribution was shifted lower numbers compared controls =.002 both diseases). Individuals ≤3 significantly higher risk developing than did individuals ⩾4 (odds ratio 3.06; 95% confidence interval 1.46–6.45). An mRNA =.033). conclusion, locus predisposes CD, most likely through diminished expression.