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• W2890771464 abstract "Acutely painful vasoocclusive crisis (VOC) is the hallmark symptom of sickle cell disease (SCD). While some patients are able to treat VOC pain with NSAIDs and oral narcotics at home and rarely use the emergency department (ED) for parenteral opioids, some patients use the ED frequently for opioid doses that often exceed ED guidelines. Some patients may experience suboptimal analgesics therapy. Others may be stigmatized as “frequent filers” or “drug seekers,” particularly when their pain cannot be objectively quantified. In this study, we examined whether CYP2C9 and CYP2C6 genotypes based on 14 allelic variants with pharmacogenetic effects on analgesic drug metabolism are associated with frequency of visits for VOC pain in a dedicated SCD ED observation pathway program. Genomic DNA from 131 adult unrelated patients with SCD was genotyped for 6 CYP2C9 alleles and 8 CYP2D6 alleles using the Sequenom Iplex Gold Reagent Kit. Theoretic metabolic profiles were based on published genetic data. We determined frequency of ED visits, including ED visits by patients ineligible for the dedicated SCD ED observation pathway due to opioid-related infractions. Based on the number of annual ED visits averaged over 5 years subjects were categorized as non-users (0 visits/year), rare-users (0-1.0 visits/year), frequent users (1.1-3.9 visits/year), or high-users (≥4 visits/year). Statistical analysis was performed using a chi-square test with significance set at p<0.05. We reported genotype frequencies as homozygous wild-type, heterozygous, and homozygous variant/compound heterozygous; and the theoretic phenotypes as extensive, intermediate, ultra-rapid, and poor metabolizers. The combined frequency of the CYP2C9 and CYP2D6 allelic variants were 0.072 and 0.302 respectively. 14% percent of the subjects were intermediate metabolizers for the CYP2C9; while 30% and 2% were intermediate and poor metabolizers respectively for the CYP2D6. For 36 subjects with 3 or more ED visits, 11 were heterozygous for impaired metabolic profiles, and 2 were homozygous for impaired metabolic profiles for the 2 genes. Of 15 patients deemed ineligible for ED observation pathway visits; 4 were heterozygous for impaired metabolic profiles and 1 was homozygous for impaired metabolic profiles for the 2 genes. Seven CYP2C9 and 20 CYP2D6 genotypes were indeterminate for the cohort. Weak associations were observed between CYP2C9 and CYP2D6 and ED visit types (p=0.75 and p=0.48 respectively). The concept of preemptive pharmacogenetics is a logical step toward identifying SCD patients with impaired drug metabolic capacities or likely to be refractory to current analgesic regimens. The integration of knowledge of genes involved in differential opioid metabolism into extant SCD standards of care could be helpful in rationalizing therapeutic practices and reducing ED visits for VOC pain." @default.
• W2890771464 created "2018-09-27" @default.
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• W2890771464 date "2018-10-01" @default.
• W2890771464 modified "2023-10-16" @default.
• W2890771464 title "248 Association of CYP2C9 and CYP2D6 Genotypes With Frequency of Emergency Department Visits for Sickle Cell Disease Acute Pain Vasoocclusive Crisis" @default.
• W2890771464 doi "https://doi.org/10.1016/j.annemergmed.2018.08.253" @default.
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