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4CPS-212 Relationship between ugt1a1*28 and serum bilirubin levels
  1. S García Gil1,
  2. R Ramos Díaz2,
  3. GJ Nazco Casariego1,
  4. MM Viña Romero3,
  5. GA González de la Fuente1,
  6. J González García1,
  7. J Ramos Rodríguez1,
  8. B del Rosario García1,
  9. F Gutiérrez Nicolás1
  1. 1Hospital Universitario de Canarias, Pharmacy, Santa Cruz de Tenerife, Spain
  2. 2Fundación Canaria de Investigación Sanitaria, Pharmacogenetic, Santa Cruz de Tenerife, Spain
  3. 3Hospital Universitario Nuestra Señora de la Candelaria, Pharmacy, Santa Cruz de Tenerife, Spain

Abstract

Background UGT1A1 polymorphisms have been relatated to interindividual variability effectiveness and toxicity in many drugs. In addition, the presence of mutated alleles in this gene has also been identified historically as Gilbert’s disease which exhibits high levels of unconjugated bilirubin.

Purpose Analysing the relationship between total serum bilirubin levels and rs8175347 (*28) polymorphism in the UGT1A1 gene.

Material and methods Observational, retrospective and unicentre study of 2 years was carried out. Patients with colorectal cancer who have been tested for gDNA determination of UGT1A1 genotype for clinical practice were included. Clinical data were obtained using the application SAP®.

A high level of total-bilirrubine was considered as at least a 90% determination, with total-bilirubin higher than 1 mg/dL.

Polymorphism *28 of UGT1A1 was established by analysing the genomic DNA of a peripheral blood sample. Genetic characterisation was carried out using the LightClycler® 480 platform and specific allele HybProbe fluorescent probes. The relationship between the UGT1A1 genotype and levels of total serum bilirrubine were determined by univariable statistical analysis. Patients were requested to sign an informed consent form prior to the inclusion.

Results One hundred and seventy-three patients were included in the study, with a median age of 62 years (81–27) and 62.3% were males. 46,2% of participants had WT genotype: 21.2% (n=17) of them showed high levels of total serum bilirubin.

On the other hand, 53.7% of patients had mutant alleles (*1/*28. *28/28), of which 36.5% (n=34) showed high levels of bilirubin (p=0.003).

Conclusion Our results show that the presence of *28 allele in UGT1A1 is associated with high levels of serum bilirubin. With these results, we feel that this finding could provide the clinician with a tool to detect patients with high risk of drug toxicity such as irinotecan or pazopanib, among others.

No conflict of interest

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