Analysis of linkage between lymphotoxin alpha haplotype and polymorphisms in 5'-flanking region of tumor necrosis factor alpha gene associated with efficacy of infliximab for Crohn's disease patients.
The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNF alpha), lymphotoxin-alpha (LT alpha) and interleukin-10 (IL-10) genes on stimulated TNF alpha and IL-10 production was studied in ulcerative colitis (UC) patients, Crohn's disease (CD) patients and in healthy controls.
In 153 patients with IBD, 64 with Crohn's disease (CD), and 89 with ulcerative colitis (UC), as well as in 54 healthy controls (HC), the frequencies of four known di-allelic polymorphisms in the genes for TNF-alpha and lymphotoxin alpha (LTalpha) were investigated.
The TNFa2b1c2d4e1 allelic combination is the strongest genetic risk factor described in CD and, with HLA class II alleles, defines a group of markers on chromosome 6 that extends from HLA class II to upstream of the TNF-beta gene.
An NcoI restriction fragment length polymorphism in the first intron of the lymphotoxin alpha gene was investigated in 35 patients with Crohn's disease, 40 patients with ulcerative colitis, and 30 unrelated healthy controls, all of Dutch origin.