Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk.
OBJECTIVE
To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies.


METHODS
DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-alpha receptor: -238 G-->A, -308 G-->A and -857C-->T, using a Taqman assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.


RESULTS
Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, c2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, c2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, c2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, c2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, c2 = 4.86, P = 0.028).


CONCLUSIONS
TNF-alpha is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-alpha promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes.
Ferguson
Lynnette R
LR
Discipline of Nutrition, the University of Auckland, Auckland, New Zealand. l.ferguson@auckland.ac.nz
Huebner
Claudia
C
Petermann
Ivonne
I
Gearry
Richard B
RB
Barclay
Murray L
ML
Demmers
Pieter
P
McCulloch
Alan
A
Han
Dug Yeo
DY
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha