Association of survivin promoter polymorphisms with inflammatory bowel disease and response to antitumor necrosis factor therapy

Genet Test Mol Biomarkers. 2015 Jun;19(6):339-43. doi: 10.1089/gtmb.2015.0036. Epub 2015 Apr 28.

Abstract

Background/aim: 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).

Material and 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.

Publication types

  • Clinical Study
  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Gene Expression
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / genetics*
  • Infliximab / therapeutic use*
  • Inhibitor of Apoptosis Proteins / blood
  • Inhibitor of Apoptosis Proteins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Survivin

Substances

  • BIRC5 protein, human
  • Biomarkers
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • Infliximab