title: The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis.
abstract: OBJECTIVE
  To test the hypothesis that children taking hydroxyurea who fail codeine therapy have an increase in reduced-functioning cytochrome P450 2D6 (CYP2D6) alleles.
  
  
  METHODS
  Children with sickle cell disease presenting to an emergency department with a pain crisis unresponsive to codeine were genotyped. The proportion of children with reduced-functioning alleles and CYP2D6 enzyme activity scores < or = 1.5, were compared, by chi2 analysis, in children taking hydroxyurea and those with mild disease.
  
  
  RESULTS
  Of the 73 children completing the study, 42 had reduced-functioning alleles; 82% of the 27 children taking hydroxyurea had reduced-functioning alleles, versus 47% of 36 those with mild disease (P < .05). Activity scores were decreased in 78% of the children taking hydroxyurea and in 44% of those with mild disease (P < .05). The odds ratios of children taking hydroxyurea were 4.9 (95% confidence interval [CI] = 1.5 to 15.9) for having reduced-functioning alleles, and 4.4 (95% CI = 1.4 to 13.4) for having a low activity score.
  
  
  CONCLUSIONS
  Failing codeine therapy for a pain crisis while taking hydroxyurea is associated with an increase in reduced-functioning CYP2D6 alleles. We recommend genetic analysis or trial of a non-CYP2D6 analgesic for these children.
authors.affiliation: Department of Pediatrics, Section of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. dbrousse@mcw.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Brousseau
authors.forename: D Gail
authors.initials: DG
authors.lastname: McCarver
authors.forename: Amy L
authors.initials: AL
authors.lastname: Drendel
authors.forename: Karthika
authors.initials: K
authors.lastname: Divakaran
authors.forename: Julie A
authors.initials: JA
authors.lastname: Panepinto
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003061:Codeine / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D000701:Analgesics, Opioid; D000986:Antisickling Agents; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine; D006918:Hydroxyurea