Polymorphisms in tumour necrosis factor and adhesion molecule genes in patients with inflammatory bowel disease: Associations with HLA-DR and -DQ alleles and subclinical markers

Background: When investigating susceptibility to inflammatory bowel disease (IBD), a multifactorial disorder with a genetic predisposition, polymorphi sms of molecules with immunoregulatory function are of potential interest. This is the first time that the polymorphisms of KLA-DR and -DQ, tumour nec rosis factor (TNF), E-selectin (CD62E), L-selectin (CD62L), and intercellul ar adhesion molecule 1 (ICAM-1, CD54) were determined in Estonians, a popul ation with a low IBD incidence rate, and their occurrence investigated in s ubgroups of a total of 53 LED patients. Methods: The reverse hybridization principle and sequence specific primers were used for HLA genotyping. To an alyse the TNF and adhesion molecule polymorphisms, the polymerase chain rea ction with subsequent restriction fragment length polymorphism or single-st rand conformation polymorphism method was used. Results: In the subgroup of antineutrophil cytoplasmic antibody (ANCA)-positive ulcerative colitis (UC ) patients we found a higher frequency of the TNF2 (20.8% versus 0.0% in AN CA-negative UC patients, P = 0.051) and HLA-DRB1*15 allele (35.4% versus 15 .7% in controls; P = 0.004). Of ANCA-positive UC patients 87.5% were carrie rs of one of these alleles (22.2% among ANCA-negative UC patients (P < 0.00 1, P-c = 0.039) and 51.4% among controls (P = 0.002). Specific typing of HL A-DRB1*15 alleles showed that the HLA-DRB1*1501 allele was responsible for the HLA-DRB1*15 association with ANCA-positive UC. Associations of ICAM-1, E-selectin, or L-selectin polymorphisms with IBD were not found. Conclusion s: TNF2 and HLA-DRB1*15 alleles were associated with ANCA-positive UC in th e investigated population. ANCA might be a useful marker, at least in some ethnic groups, for dividing IBD patients into genetically more homogeneous subgroups.