DISTRIBUTION OF 4 POLYMORPHISMS IN THE TUMOR-NECROSIS-FACTOR (TNF) GENES IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE (IBD)

In 153 patients with IBD, 64 with Crohn's disease (CD), and 89 with ul cerative colitis (UC), as well as in 54 healthy controls (HC), the fre quencies of four known di-allelic polymorphisms in the genes for TNF-a lpha and lymphotoxin alpha (LT alpha) were investigated. In the Dutch population, the alleles of these four polymorphisms are present in onl y five combinations, called TNF haplotypes: TNF-C, -E, -H, -I, -P. Fur thermore, the relation with the presence of perinuclear anti-neutrophi l cytoplasmic autoantibodies (P-ANCA) was studied. A small, but statis tically significant, association between the polymorphism at position -308 in the promoter region of the TNF-alpha gene and UC was found. Th e frequency of the uncommon TNF-alpha-308 allele 2 was found to be dec reased in patients with UC compared with HC (allele frequency of allel e 2 in UC patients 0.15 versus 0.25 in HC, P = 0.044). No significant differences in distribution of the TNF haplotypes were found between I BD patients and HC, although there was a tendency towards a higher fre quency of the TNF-C haplotype in UC patients compared with controls (h aplotype frequency 22% versus 13%; P = 0.19). No statistically signifi cant differences in distribution of the TNF haplotypes were observed b etween P-ANCA-positive and P-ANCA-negative UC patients. The strength o f the associations indicates that TNF genes are not markers for the pr edisposition to suffer from IBD. They may, however, be markers of subs ets of patients with UC and CD.