[TNF- alpha gene polymorphisms in rheumatoid arthritis patients treated with anti-TNF-alpha agents: preliminary results].
OBJECTIVE
To study -238 and +489 TNF-alpha polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA).


METHODS
We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment length polymorphism procedure. Several clinical and serological parameters were also examined.


RESULTS
Severe RA patients disclosed the -238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy.


CONCLUSIONS
The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus -238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.
Fabris
M
M
Divisione di Reumatologia, DPMSC, Università degli Studi di Udine, Italia.
Di Poi
E
E
Sacco
S
S
Damante
G
G
Sinigaglia
L
L
Ferraccioli
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008727:Methotrexate