Tu1942 Genetic Variants At FCGR2A and 13q12 Are Associated With Disease Couse in Ulcerative Colitis

Abstract

G A A b st ra ct s loss of response to anti-TNFα therapy after one year. The cause of this limited efficacy is unclear, but past studies hypothesized that the individual variation of drug metabolism may play an important role. Thus, given the limited data available, the role of Fcγ IIIa receptor (i.e. one of the four receptors involved in the catabolic pathway of anti-TNF-α drugs) polymorphisms should be further explored. Aim: The aim of this prospective, long-term follow up study was to evaluate the correlation between Fcγ IIIa receptor polymorphisms and clinical outcome in IBD patients undergoing biologic therapy. Methods: We enrolled consecutive IBD patients who achieved clinical remission by anti-TNF-α therapy. Blood samples were collected at the beginning of biological therapy. The assessment of IBD activity was based on the Harvey-Bradshaw Index score (HBI, remission 16) for CD patients and on the Mayo score (Mayo<2 remission, mild disease 2-5, moderate/severe disease 6-12) for UC patients. Biochemical evaluation and clinical score were assessed every 8 weeks. For the genotyping analysis we used a Light Snips (Tib-Molbiol, Genova, Italy) and the Real-Time PCR Technique developed by Light Cycler 480 Instrument (Roche, Mannheim, Germany). Results: We prospectively included 39 patients (12UC/27 CD, 16F/23M) with a median follow-up of 66.8 weeks (10112). A total of 25 (64.1%) (10UC/15CD) patients kept in remission during the whole follow up period, while 14 (35.9%) (2UC/12CD) experienced disease relapse. As shown in the Table, four out of 14 (28.6%) (1UC/3CD) patients who experienced disease relapse, had FcγIIIa-158 V/V receptor polymorphism, while the remaining 10 (71.4%) (9CD/1UC) had FcγIIIa-158 F/V or F/F receptor polymorphisms. Out of 25 patients who kept in remission, 3 (12%) (1CD/2UC) had FcγIIIa-158 V/V receptor polymorphism, whereas the remaining 22 (88%) (14CD/8UC) showed FcγIIIa-158 F/V or F/F receptor polymorphisms. Patients in remission tended to have more often FcγIIIa-158 V/V receptor polymorphism compared to patients who relapsed, but statistical significance was not reached. Conclusion: The evaluation of Fcγ IIIa-158 V/V receptor polymorphism does not seem useful in identifying patients who are more likely to lose anti TNF-α response during a long term period. However, further larger studies are necessary to investigate the role of Fcγ IIIa receptor polymorphisms