Tumor necrosis factor receptor superfamily, member 1B haplotypes increase or decrease the risk of inflammatory bowel diseases in a New Zealand caucasian population

Abstract

Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role that selected single nucleotide polymorphisms (SNPs) and haplotypes in the TNF-alpha receptor (TNSFRSF1B) gene play in the risk of IBD in a New Zealand Caucasian population. DNA samples from 388CD, 405UC, 27 indeterminate colitis patients, and 293 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in TNSFRSF1B: rs1061622 (c.676T>C), rs1061624 (c.*gt;G), and rs3397 (c.* 1690T>C), using TaqMan technologies. Carrying the rs1061624 variant decreased the risk of UC in the left colon (OR 0.73, 95 CI=0.54 -1.00) and of being a smoker at diagnosis (OR 0.62; 95 CI=0.40 -0.96). Carrying the rs3397 variant decreased the risk of penetrating CD (OR 0.62, 95 CI=0.40 -0.95). Three marker haplotype analyses revealed highly significant differences between CD patients and control subjects ( X2 =29.9, df=7, P=.0001) and UC cases and controls (X2 =46.3, df=7, P