Cheedy Jaja

Cytochrome p450 enzyme polymorphism frequency in indigenous and native american populations: a systematic review.

Objective: The purpose of our study was to evaluate the evidence on the prevalence of cytochrome P450 enzyme polymorphisms as potential genetic factors influencing drug efficacy and safety in the indigenous populations of the American hemispheres. Methods: We conducted a systematic review of studies published between 1985 and 2006 using the Pubmed database. Results: We identified only 10 original research studies on CYP2A6, CYP2D6, CYP2C9, CYP2C19 and CYP2E1 in 13 indigenous American populations. Interethnic differences in the frequency of CYP450 genetic variants existed both among the examined indigenous populations and in comparison with African, Asian and European populations. Conclusions: There are surprisingly few data on CYP450 enzyme polymorphisms in indigenous American populations, and it is difficult to draw any clear inferences about how these populations might be expected to respond to drugs in relation to other racial or ethnic groups. This lack of information could create a barrier to the use of pharmacogenetic testing in these populations. Collaborative partnerships between indigenous communities and researchers are needed to avail the clinical benefits of CYP450 enzyme polymorphism testing to indigenous populations.

CYP2C9 Allelic Variants and Frequencies in a Pediatric Sickle Cell Disease Cohort: Implications for NSAIDs Pharmacotherapy

Nonsteroidal anti‐inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism‐PCR assays and the Tag‐It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate‐specific effects of variant alleles common in populations with genetic susceptibility to SCD.

Advancing Genomic Research and Reducing Health Disparities: What Can Nurse Scholars Do?

PURPOSE Advances in genomic research are improving our understanding of human diseases and evoking promise of an era of genomic medicine. It is unclear whether genomic medicine may exacerbate or attenuate extant racial group health disparities. We delineate how nurse scholars could engage in the configuration of an equitable genomic medicine paradigm. ORGANIZING CONSTRUCT We identify as legitimate subjects for nursing scholarship the scientific relevance, ethical, and public policy implications for employing racial categories in genomic research in the context of reducing extant health disparities. FINDINGS Since genomic research is largely population specific, current classification of genomic data will center on racial and ethnic groups. Nurse scholars should be involved in clarifying how putative racial group differences should be elucidated in light of the current orthodoxy that genomic solutions may alleviate racial health disparities. CONCLUSIONS Nurse scholars are capable of employing their expertise in concept analysis to elucidate how race is used as a variable in scientific research, and to use knowledge brokering to delineate how race variables that imply human ancestry could be utilized in genomic research pragmatically in the context of health disparities. CLINICAL RELEVANCE In an era of genomic medicine, nurse scholars should recognize and understand the challenges and complexities of genomics and race and their relevance to health care and health disparities.

Preemptive genotyping of CYP2C8 and CYP2C9 allelic variants involved in NSAIDs metabolism for sickle cell disease pain management

Interindividual variability in analgesic effects of nonsteroidal anti‐inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the CYP2C8 and CYP2C9 enzymes. We described CYP2C8 and CYP2C9 genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for seven CYP2C8 and 15 CYP2C9 alleles using the iPLEX ADME PGx multiplexed panel. CYP2C8*1 (0.806),*2 (0.164), *3 (0.018), and *4 (0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively. CYP2C9*1 (0.824), *2 (0.027), *3 (0.012), *5 (0.009), *6 (0.009), *8 (0.042), *9 (0.061), and *11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty‐two and 55 subjects, respectively had at least one variant CYP2C8 or CYP2C9 allele. Although the distribution of the CYP2C9 (p = 0.0515) phenotypes was marginally significantly in high and low ED users; some CYP2C8 and CYP2C9 allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. CYP2C8 and CYP2C9 preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.

Advancing genomic research and reducing health disparities

PURPOSE Advances in genomic research are improving our understanding of human diseases and evoking promise of an era of genomic medicine. It is unclear whether genomic medicine may exacerbate or attenuate extant racial group health disparities. We delineate how nurse scholars could engage in the configuration of an equitable genomic medicine paradigm. ORGANIZING CONSTRUCT We identify as legitimate subjects for nursing scholarship the scientific relevance, ethical, and public policy implications for employing racial categories in genomic research in the context of reducing extant health disparities. FINDINGS Since genomic research is largely population specific, current classification of genomic data will center on racial and ethnic groups. Nurse scholars should be involved in clarifying how putative racial group differences should be elucidated in light of the current orthodoxy that genomic solutions may alleviate racial health disparities. CONCLUSIONS Nurse scholars are capable of employing their expertise in concept analysis to elucidate how race is used as a variable in scientific research, and to use knowledge brokering to delineate how race variables that imply human ancestry could be utilized in genomic research pragmatically in the context of health disparities. CLINICAL RELEVANCE In an era of genomic medicine, nurse scholars should recognize and understand the challenges and complexities of genomics and race and their relevance to health care and health disparities.

(281) Genetic variability of UGT2B7, CYP3A4, CYP3A5 and CYP2B6 DMETs in a sickle cell disease patient cohort

results suggest that the induction of CD163 via mPEI nanoparticles can shift the phenotype to an anti-inflammatory profile in human macrophages under different inflammatory conditions. This translational approach could be useful to specifically target macrophages in chronic inflammatory conditions such as invasive surgeries to prevent the development of chronic pain. Supported by Rita Allen Foundation & American Pain Society 2011 Pain grant (AR-S); National Institutes of Health, NIGMS, R15GM109333 (AR-S). PRSI program 2014 and 2015, Presbyterian College School of Pharmacy (AA, LB and DF).