Naslov
Association of polymorphisms in promoter region of TNF-α -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy

Autori
Miler, Marijana ; Nikolac Gabaj, Nora ; Ćelap, Ivana ; Grazio, Simeon ; Tomašić, Vedran ; Bišćanin, Alen ; Mitrović, Joško ; Đerek, Lovorka ; Morović- Vergles, Jadranka ; Vrkić, Nada ; Štefanović, Mario

Izvornik
Rheumatology international (0172-8172) 41 (2021); 2195-2203

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
adalimumab ; C-reactive protein ; fecal calprotectin ; immune-mediated rheumatic diseases ; infiximab ; infammatory bowel diseases ; TNF-α polymorphisms

Sažetak
The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune- mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer’s instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223 ; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4–39.6) vs 3.1 (1.5–6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25–552) vs 20 (20–20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti- TNF drugs were not associated with TNF-α -238 and -308 polymorphisms.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

POVEZANOST RADA