title: Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis.
abstract: Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93-80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage.
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: J L
authors.initials: JL
authors.lastname: Thijs
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: B A M
authors.initials: BAM
authors.lastname: Van Der Geest
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: J
authors.initials: J
authors.lastname: Van Der Schaft
authors.affiliation: b Department of Clinical Pharmacy.
authors.forename: M P
authors.initials: MP
authors.lastname: Van Den Broek
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: W O
authors.initials: WO
authors.lastname: Van Seggelen
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: C A F
authors.initials: CAF
authors.lastname: Bruijnzeel-Koomen
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hijnen
authors.affiliation: c Department of Clinical Chemistry and Hematology , University Medical Center Utrecht , Utrecht , the Netherlands.|d Department of Clinical Chemistry , Erasmus University Medical Center Rotterdam , Rotterdam , the Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: Van Schaik
authors.affiliation: a Department of Dermatology and Allergology.
authors.forename: M S
authors.initials: MS
authors.lastname: De Bruin-Weller
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; C000715591:UGT1A9 protein, human; D016572:Cyclosporine; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D009173:Mycophenolic Acid
keywords: Atopic dermatitis; UGT1A9; mycophenolic acid; pharmacogenomics