Tumor necrosis factor receptor superfamily, member 1B haplotypes increase or decrease the risk of inflammatory bowel diseases in a New Zealand caucasian population.
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 388 CD, 405 UC, 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.*1663A > 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 (chi(2) = 29.9, df = 7, P = .0001) and UC cases and controls (chi(2) = 46.3, df = 7, P < .0001). We conclude that carrying a 3-marker haplotype in the TNSFRSF1B gene may increase (e.g., haplotype of GGC was 2.9-fold more in the CD or UCpatients) or decrease (e.g., TGT was 0.47-fold less in UC patients) the risk of IBD in a New Zealand Caucasian population.
Discipline of Nutrition, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand. l.ferguson@auckland.ac.nz
Lynnette R
LR
Ferguson
Dug Yeo
DY
Han
Claudia
C
Huebner
Ivonne
I
Petermann
Murray L
ML
Barclay
Richard B
RB
Gearry
Alan
A
McCulloch
Pieter S
PS
Demmers