Tumor necrosis factor gene polymorphisms in ankylosing spondylitis.

Despite the strength of the association of ankylosing spondylitis (AS) with HLA-B27, other genetic elements could play a possible role in the pathophysiology of AS. In view of its gene location, in the proximity of the HLA-B locus, and biological effects, tumor necrosis factor (TNF) genes are potential candidates for additive susceptibility factors to AS. TNFalpha and TNFbeta genotypes were analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B*27-positive controls. No significant differences of TNFalpha promoter variations at position -308 and -238 were found in AS patients in comparison with controls. The -244 polymorphism was not detected in our population. The TNFbeta genotype frequency was significantly different between AS patients and random controls. However, when the distribution of the TNFbeta genotype was compared in B*27-positive AS patients and controls, these differences disappeared. In addition, we demonstrated that the TNFbeta*1 was in strong linkage disequilibrium with the B*27 allele, which may explain the differences observed for the TNFbeta genotype among AS patients and random controls. Our data suggest that the polymorphisms of TNFalpha and TNFbeta genes do not have an independent effect on AS susceptibility.