Srpski arhiv za celokupno lekarstvo 2011 Volume 139, Issue 11-12, Pages: 784-789
https://doi.org/10.2298/SARH1112784S
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Association of TNF-alpha polymorphism (-308 A/G) with high activity of rheumatoid arthritis and therapy response to etanercept
Stojanović Sonja (Institut za lečenje i rehabilitaciju „Niška Banja”, Niška Banja)
Jevtović-Stoimenov Tatjana (Katedra za biohemiju, Medicinski fakultet, Niš)
Stanković Aleksandra (Institut za lečenje i rehabilitaciju „Niška Banja”, Niška Banja)
Pavlović Dušica (Katedra za biohemiju, Medicinski fakultet, Niš)
Nedović Jovan (Institut za lečenje i rehabilitaciju „Niška Banja”, Niška Banja)
Stamenković Bojana (Institut za lečenje i rehabilitaciju „Niška Banja”, Niška Banja)
Dimić Aleksandar (Institut za lečenje i rehabilitaciju „Niška Banja”, Niška Banja)
Marinković Milena (Katedra za biohemiju, Medicinski fakultet, Niš)
Introduction. Genetic markers are significant predictive factors in the
assessment of therapeutic response of rheumatoid arthritis (RA) to
biological medication. Objective. The aim of the study was to determinate
the association of TNF-α -308 G/A polymorphism with a high RA activity and
its predictive value in therapeutic response after 12 months of treatment
with Etanercept. Methods. The study enrolled 132 patients with RA treated
with Methotrexate (MTX) and 58 control subjects. The -308 TNF polymorphism
was examined using the polymerase chain reaction - restriction fragment
length polymorphism (PCR- RFLP). The patients were divided into two groups:
group A with A/A and A/G genotype and group G with G/G genotype. After 12
months, beside MTX, Etanercept was introduced in 36 patients. We compared
clinical activity among the groups at the beginning and after one year of
therapy by using DAS28 SE (Disease activity score with sedimentation).
Results. There was no significant difference found in the distribution of G
and A allele in the RA group compared to the control group. A significantly
higher disease activity was noticed in A compared to the G group (DAS28 SE:
6.31 to 5.81; p<0.05). The patients with A allele kept the majority of the
disease activity even after a year of study (DAS28 SE: 5.25 to 3.89). After
a year of MTX and Etanercept therapy, a significantly larger proportion of
patients in the G group displayed a good clinical response to treatment
compared to the A group (81.5% to 25%; p<0.05). The average change of DAS28
SE in G group was 2.24, while in the A group DAS 28 reduction was
significantly lower (1.17; p=0.005). Conclusion. There was no significant
difference in the frequency of A in the patients with RA compared to healthy
subjects. The presence of A allele is associated with more serious clinical
presentation of the disease and lower therapeutic response to Etanercept.
Keywords: polymorphism of genes, TNF-α, rheumatoid arthritis