Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn's disease.
OBJECTIVE
To investigate the correlation between rs1568885, rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn's disease (CD).


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 2(nd) 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. χ (2) 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.


CONCLUSIONS
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.
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Diamantis
D
Thomas
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Maria
M
Gazouli
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Theodoros
T
Karantanos
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Stella
S
Rigoglou
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Georgios
G
Karamanolis
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Konstantinos
K
Bramis
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
George
G
Zografos
Diamantis Thomas, Theodoros Karantanos, Konstantinos Bramis, George Zografos, George E Theodoropoulos, Colorectal Unit, 1 Department of Propaedeutic Surgery, "Hippokrateio" Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
George E
GE
Theodoropoulos
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003113:Colonoscopy; D058966:Contactins / Q000235:genetics*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D004334:Drug Administration Schedule; D004724:Endoscopy; D005260:Female; D005838:Genotype; D006115:Greece; D006801:Humans; D007249:Inflammation; D000069285:Infliximab; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
D000911:Antibodies, Monoclonal; D015415:Biomarkers; C000595918:CNTN5 protein, human; D058966:Contactins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab
Crohn’s disease; Infliximab; Polymorphisms; Treatment response