Innate immunogenetics and nflammatory bowel disease (IBD)

significantly increased transmission of the -94delATTG (deletion) allele from parents to IBD offspring (Table ).Evidence was proportionately strongest in non-Jewish, UC trios, and compared to unrelated controls, UC trio probands had signficantly greater -94delATTG deletion homozygote genotypes.To replicate these findings we then genotyped 383 new non-Jewish UC patients without parental samples and 653 new non-Jewish Caucasian controls from New York.These new UC patients also had greater homozygote deletion genotypes (21.5%) vs. controls (15.0%,p = 0.011).As determined by electrophoretic mobility shift assays (EMSA), nuclear proteins from human colon and epithelial cell lines bound 32P labeled wildtype but not -94delATTG containing ofigonucleotides.Furthermore, in preliminary experiments -94delATTG luciferase constructs transfected in HELA cells stimulated by lipopolysaccharide shQwed altered promoter activity as compared to wildtype constructs.Conclusions: Homozgotes of a 4 bp NFKB1 deletion promoter polymorphism with altered nuclear protein binding and promoter activity are at significantly greater risk for UC.TDT of-94d~TTG all~ 4BD