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 th e pathophysiology of AS. In view of its gene location, in the proximit y of the HLA-B locus, and biological effects, tumor necrosis factor (T NF) genes are potential candidates for additive susceptibility factors to AS. TNF alpha and TNF beta genotypes were analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B27-positive cont rols. No significant differences of TNF alpha promoter variations at p osition -308 and -238 were found in AS patients in comparison with con trols. The -244 polymorphism was not detected in our population. The T NF beta genotype frequency was significantly different between AS pati ents and random controls, However, when the distribution of the TNF be ta genotype was compared in B27-positive AS patients and controls, th ese differences disappeared. In addition, we demonstrated that the TNF beta1 was in strong linkage disequilibrium with the B*27 allele, whi ch may explain the differences observed for the TNF beta genotype amon g AS patients and random controls Our data suggest that the polymorphi sms of TNF alpha and TNF beta genes do not have an independent effect on AS susceptibility.