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4CPS-147 Determination of tpmt and nudt15 polymorphisms in a patient with common variable immunodeficiency
  1. S García Gil1,
  2. M Carrillo Palau2,
  3. V Casañas Sánchez3,
  4. R Ramos Diaz3,
  5. F Gutiérrez Nicolás1,
  6. GJ Nazco Casariego1,
  7. P Yanes Sánchez4,
  8. MM Viña Romero5
  1. 1Hospital Universitario de Canarias, Pharmacy, Santa Cruz de Tenerife, Spain
  2. 2Hospital Universitario de Canarias, Gastroenterology, Santa Cruz de Tenerife, Spain
  3. 3Fundación Canaria de Investigación Sanitaria, Biology, Santa Cruz de Tenerife, Spain
  4. 4Universidad de la Laguna, Pharmacy, Santa Cruz de Tenerife, Spain
  5. 5Hospital Universitario Nuestra Señora de la Candelaria, Pharmacy, Santa Cruz de Tenerife, Spain


Background The lack of activity in thiopurine-methyltrasnferase (TPMT) is related to severe toxicity in the use of thiopurines (azathioprine, 6-mercaptopurine and thioguanine). This lack of activity is often due to genetic polymorphisms located at TPMT, and recently demonstrated in NUDT15 genes.

Purpose To describe the case of a patient with inflammatory elbow disease (IBD) and a congenital immunodeficiency who is being prescribed azathioprine and who has been tested for TPMT and NUDT15 genetic polymorphisms determination.

Material and methods Male, 21-years-old patient who was diagnosed at the age of eight years with common variable immunodeficiency (CVI) with gastrointestinal manifestations. In 2002 the patient was diagnosed with ulcerative jejunitis and after receiving different first-line treatments (mesalazine and corticosteroid) was not able to obtain a good control of the disease. Thus, his doctor decided to start treatment with azathioprine.

Given the risk of severe immunosuppression derived from the CVI and the use of azathioprine the decision was taken to make a genetic polymorphism analysis of TPMT (rs2842934, rs2842934, rs1800460, rs1800584 and rs1142345) and NUDT15 (rs116855232, rs147390019, rs554405994 and rs186364861).

DNAg was carried out using the Ramos et al. (2015) method and the characterisation was implemented using PCR and DNA sequencing.

Results The patient showed a wild-type genetic profile for the polymorphism analysed. Consequently, he was prescribed with azathioprine with a complete dosage of 100 mg per day (2 mg/kg/d).

After 3 months of treatment the patient had maintained a neutrophil normal range (higher than 2000 neutrophils per mm3) and, in addition, achieved a good control of the illness. Therefore the patient continued with the azathioprine at the usual dosage.

Conclusion The integration of pharmacy services in the multidisciplinary teams is facilitating the implementation of pharmacogenetics in daily clinical practice in our hospitals. This kind of determinations provides the prescription clinicians with tools to improve the effectiveness and safety of treatments.

In this case we have given an example in which the determination of a genetic WT profile for TPMT and NUDT15 has allowed for the full use of azathioprine dosage from the beginning of the treatment, which therefore resulted in an adequate control of the disease.

No conflict of interest

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