Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Dissertation committee:
Ζωγράφος Γεώργιος Καθηγητής Ιατρική Σχολή ΕΚΠΑ
Κυριακοπούλου-Λυμπέρη Μαρία Καθηγήτρια Ιατρικής Σχολής ΕΚΠΑ
Γαζούλη Μαρία Αν. Καθηγήτρια Ιατρική Σχολή ΕΚΠΑ
Θεοδωρόπουλος Γεώργιος Αν. Καθηγητής Ιατρική Σχολή ΕΚΠΑ
Μαρίνος Ευάγγελος Αν. Καθηγητής Ιατρική Σχολή ΕΚΠΑ
Καραμανώλης Γεώργιος Επίκουρος Καθηγητής Ιατρική Σχολή ΕΚΠΑ
Παπανικολάου Ιωάννης Επίκουρος Καθηγητής Ιατρική Σχολή ΕΚΠΑ
Original Title:
Φαρμακογενωμική ανάλυση ασθενών με Ιδιοπαθή φλεγμονώδη νόσο του εντέρου (ΙΦΝΕ) και συσχέτιση με ανταπόκριση στους αντι-TNF παράγοντες
Summary:
Idiopathic inflammatory bowel diseases are multifactorial diseases without a particular infectious or environmental cause. IBD comprise two major disorders: ulcerative colitis and Crohn's disease. The pharmaceutical agents that are used for the treatment of IBD include aminosalicylates, corticosteroids, antibiotics, immunosuppressants, and in recent years, biological therapies which include the anti-TNF agents. However, because of the great heterogeneity in patients’ response, there is need to highlight markers that are able to predict this response. Such biomarkers are genes polymorphisms and the present study aims to investigate the genetic polymorphisms in IBD associating them with patients’ response in anti-TNFα therapy.
Methods
One hundred and twenty-six patients diagnosed with CD based on standard clinical, endoscopic, radiological, and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the 1st Department of Propaedeutic Surgery. Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0, 2, 6 and then every 8 wk. Clinical and serological responses were assessed using the Harvey- Bradshaw Index and serum C-reactive protein (CRP) levels, respectively, and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions. χ2 test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies.
Results
Eighty patients (63.49%) were classified as complete and 32 (25.39%) as partial responders to infliximab, while 14 (11.11%) were primary non-responders. No correlation was found between response to infliximab and patients’ characteristics such as age, gender and disease duration. There was consistency between Harvey-Bradshaw index scores and serum CRP levels. The TT genotype of the rs1568885 polymorphism was significantly related to partial response (P = 0.024) and resistance to infliximab (P = 0.007) while the AT genotype was more frequent in partial responders (P = 0.035) and in primary non-responders (P = 0.032). Regarding rs1813443, the CC genotype was found to be associated with partial response (P = 0.005) and primary resistance (P = 0.002) to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab.
Conclusion
Based on our results, the rs1568885 and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn’s disease
Main subject category:
Health Sciences
Keywords:
Crohn Disease, Ulcerative Colitis, anti-TNF, Polymorphisms,Infliximab
Number of references:
285
File:
File access is restricted only to the intranet of UoA.
διπλωμ 1.3.pdf
1 MB
File access is restricted only to the intranet of UoA.
