Association of survivin promoter polymorphisms with inflammatory bowel disease and response to antitumor necrosis factor therapy.
OBJECTIVE
Recent evidence suggests that survivin, a member of the inhibitors of apoptosis family that prevents cell death and regulates cell division is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to identify a possible association between individual genetic variation, IBD susceptibility, and response to infliximab (IFX).


METHODS
The expression levels of survivin were detected in pathologic areas of fresh tissues and blood samples by real-time reverse transcriptase - polymerase chain reaction (RT-PCR) from IBD patients. Polymorphisms were identified using the polymerase chain reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Clinical and endoscopic response to IFX was evaluated by ileocolonoscopy performed at baseline and after 12-20 weeks of therapy with patients classified as either responders or nonresponders.


RESULTS
No significant differences were found between survivin mRNA levels between patients and controls. Significant differences in both allele and genotype frequencies between Crohn's disease (CD) and ulcerative colitis (UC) patients and controls were found in -31C/G polymorphism. No association with IBD development was found for the -625G/C and -241T/C polymorphisms, since those polymorphisms were overrepresented in a healthy population. Additionally no significant association was found between -31C/G polymorphism and the clinical response of CD patients to IFX.


CONCLUSIONS
Survivin promoter polymorphism -31C/G might influence the susceptibility to IBD in the Greek population, but not the CD patient's response to anti-TNF drugs.
1 Laboratory of Biology , Department of Basic Medical Sciences, School of Medicine, University of Athens, Athens, Greece .
Emmanouela
E
Rapti
1 Laboratory of Biology , Department of Basic Medical Sciences, School of Medicine, University of Athens, Athens, Greece .
Maria
M
Gazouli
1 Laboratory of Biology , Department of Basic Medical Sciences, School of Medicine, University of Athens, Athens, Greece .
Evangelia
E
Legaki
2 Second Department of Surgery, Aretaieion Hospital, Medical School, University of Athens , Athens, Greece .
George
G
Karamanolis
1 Laboratory of Biology , Department of Basic Medical Sciences, School of Medicine, University of Athens, Athens, Greece .
Diamantis
D
Thomas
1 Laboratory of Biology , Department of Basic Medical Sciences, School of Medicine, University of Athens, Athens, Greece .
Evangelos
E
Marinos
2 Second Department of Surgery, Aretaieion Hospital, Medical School, University of Athens , Athens, Greece .
Ioannis
I
Papaconstantinou
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D000069285:Infliximab / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000077022:Survivin
C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D000069285:Infliximab