Personalizing Pain Management in Sickle Cell Disease: A Pilot Study in the Cytochrome P450 2D6 Gene Polymorphisms in Pediatric Sickle Cell Disease Open Access

Harrington, Rosiland Kay (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/1544bp24s?locale=en
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Abstract

Introduction:

Opioid analgesic medications are used in patients with sickle cell disease (SCD) for the treatment of vaso-occlusive crisis (VOC). Oral opioids require enzymatic modification by the CYP2D6 enzyme to become active analgesic compounds. The CYP2D6 gene is highly polymorphic with varying degrees of activity from ultra rapid to no activity. The primary objective of this study is to determine the prevalence of cytochrome P450 CYP2D6 gene polymorphisms in a large sickle cell patient population.

Methods:

Patients were screened to determine eligibility at the time of routinely scheduled well-visit in Sickle Cell Clinic. Once consent and/or assent were obtained, the patient's medical history and medical record was reviewed to record the documented hemoglobinopathy. Whole blood samples were analyzed using CYP2D6 genotyping assay. The Luminex xTagTM assay system was used for PCR amplification of 12 small nucleotide polymorphisms (SNPs) and two gene rearrangements.

Results:

This was a prevalence study to determine the ratio of CYP2D6 polymorphisms among pediatric patients with SCD recruited from the Comprehensive Sickle Cell Program of Children's Healthcare of Atlanta at Egleston Hospital. The greatest percentage of patients genotyped were intermediate metabolizers (50%) compared to those who were poor metabolizers (19.74%), extensive metabolizers (18.42%) and ultra-rapid metabolizers (11.84%).

Conclusions:

The intermediate metabolizers were the dominant variant among the patients tested rather than the poor metabolizers as we had proposed at the beginning of the study. Although the poor metabolizers were not the majority, the percentage of 19.74 put them at the upper limit of the range given for the black adult population. Because intermediate metabolizers dominate the study population and are noted for a reduction of function of the CYP2D6 enzyme, this may contribute to the poor drug efficacy and hospitalizations in this pediatric population.

Table of Contents

TABLE OF CONTENTS I.Introduction II.Background III.Methods IV.Results V.Discussion VI.References VII.Tables a. Table 1: Demographic and Clinical Characteristics for Subjects Genotyped (n=76) b. Graph 1: Patients by Hemoglobin S Variant subdivided by Metabolizer Phenotype c. Graph 2: Patients by Metabolizer Phenotype subdivided by Hemoglobin S Variant d. Table 2: Comparison of Mean Hospitalization Variables for Poor Metabolizers and All Other Groups (Intermediate, Extensive and Ultra-Rapid Metabolizers) e. Table 3: Comparison of Mean Hospitalization Variables for Poor and Intermediate Metabolizers versus Extensive and Ultra-Rapid Metabolizers f. Graph 3: Comparison of Disease severity between Patients Hospitalized for Pain and Patients with Unknown Pain Status g. Table 4: Comparison of Clinical Characteristics of Patients Hospitalized for Pain (n=43) to Patients with Unknown Pain Status (n=33)


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