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 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 (χ 2 = 29.9, df = 7, P = .0001) and UC cases and controls (χ 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.
Highlights
Inflammatory bowel diseases (IBDs), including Crohn disease (CD) and ulcerative colitis (UC), provide a good example of a disorder for which there is compelling evidence for genetically determined susceptibility that interacts with environmental factors, including microbiota and diet [1]
This study considers the role of three single nucleotide polymorphisms (SNPs) in TNFRSF1B Table 1 on the overall risk or phenotype of IBD in a New Zealand Caucasian population, recruited from the Canterbury region in New Zealand [5] 2006
The present results show that carrying a single variant allele in TNFRSF1B c.676T > C, 1663A > G, or 1690T > C has no significant effect on the overall risk of either CD or UC
Summary
Inflammatory bowel diseases (IBDs), including Crohn disease (CD) and ulcerative colitis (UC), provide a good example of a disorder for which there is compelling evidence for genetically determined susceptibility that interacts with environmental factors, including microbiota and diet [1]. We have previously associated polymorphisms in several genes including NOD1&2, TLR4, DLG5, ATG16L1, and IL23R with risk of IBD in New Zealand [6,7,8,9,10,11,12], these only increase the IBD risk to a small extent and cannot explain the high New Zealand disease incidence. This study considers the role of three SNPs in TNFRSF1B Table 1 on the overall risk or phenotype of IBD in a New Zealand Caucasian population, recruited from the Canterbury region in New Zealand [5] 2006. These SNPs were previously associated with CD risk in other populations [22, 23]
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