TUMOR-NECROSIS-FACTOR-ALPHA GENE POLYMORPHISMS IN RHEUMATOID-ARTHRITIS - ASSOCIATION WITH SUSCEPTIBILITY TO, OR SEVERITY OF, DISEASE

Genetic factors associated with rheumatoid arthritis (RA) might involv e variant tumour necrosis factor (TNF)-alpha genes. Therefore, polymor phisms at positions -308, -238, -376, -163 and +70 relative to the tra nscription initiation site were studied with respect to the susceptibi lity to, or severity of, RA. TNF-alpha genotypes of 283 RA patients an d 116 healthy individuals were determined. Clinical data were obtained from patient files and questionnaires. The distribution of TNF-alpha alleles was similar in RA patients and healthy controls. With respect to disease severity, the TNF-alpha -238GA genotype was found to be ass ociated with the absence of erosions [odds ratio (OR) 4.1, confidence interval 1.0-17]. In addition, this genotype was associated with a low er number of hand joints affected by erosions within the first 3 yr of disease onset compared to -238GG. The association between the -238 po lymorphism and radiographic progression was independent of the presenc e of HLA-DR4. In line with this observation, the OR for the presence o f erosions in patients with both risk factors (DR4 and -238GG) compare d to patients who lack these factors was 11.1 (1.8-6.8). No associatio ns between the TNF-alpha - 308, +70 and -376 alleles and susceptibilit y to, or severity of, RA could be demonstrated. Our data indicate that the TNF-alpha -238GA genotype is associated with decreased radiologic ally detectable progression of RA.