Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine

Ahmed, Shabbir; Zhou, Zhan; Zhou, Jié; Chen, Shuqing

doi:10.1016/j.gpb.2016.03.008

Cited by 259 publications

(185 citation statements)

References 173 publications

(194 reference statements)

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“…This observation is in agreement with a previously published study . The frequencies of *1/*2 , *2/*2 and *2/*3 genotypes are higher in Caucasians compared with Asians . This implies that SEEA individuals with defective genotypes may experience less clinically significant consequences following treatment with drugs that are substrates of CYP2C9.…”

Section: Discussionsupporting

confidence: 93%

“…CYP2C9 : Among the CYP2C subfamily, CYP2C9 is the most abundantly expressed (18% of total hepatic CYP protein) and significantly contributes to biotransformation of about 15%‐25% of commonly used drugs including anticoagulants ( S‐ warfarin and S ‐acenocoumarol), antihypertensives (losartan and irbesartan), NSAIDs (celecoxib, diclofenac, ibuprofen and indomethacin), oral hypoglycaemics (glipizide and tolbutamide), anticonvulsants (phenytoin and valproate), psychotropics (amitriptyline), proton pump inhibitors (omeprazole and lansoprazole), and antimicrobials (metronidazole and ritonavir) . Interindividual variability in CYP2C9 expression and activity could therefore impact therapeutic efficacy and safety of these drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Significant variability in drug response exists concerning efficacy, optimal dose and adverse drug reactions. Genetic variations have been estimated to contribute about 20%‐30% to this variability . Interindividual variability in genotype frequencies associated with variability in drug response has been reported in various ethnic populations.…”

Section: What Is Known and Objectivementioning

confidence: 99%

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CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

2019

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Summary What is known and objective Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug‐metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South‐East and East Asian (SEEA) populations. Methods Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. Results and discussions A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%‐99.1%), *1/*3 (2.3%‐20.1%) and *3/*3 (0%‐2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%‐88.07%), *1/*2 (21.5%‐86.46%), *1/*3 (0.8%‐15.8%), *2/*2 (3.4%‐14.5%), *2/*3 (0%‐7.3%) and *3/*3 (0%‐10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%‐69.6%), *1/*1 (0%‐61.21%) and *1/*10 (0%‐62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%‐71.4%), *1/*3 (16.0%‐57.1%) and *1/*1 (0%‐82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). What is new and conclusion Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South‐East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South‐East Asian countries which will assist in establishing the databases for SEEA populations.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: What Is Known and Objectivementioning

confidence: 99%

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CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

2019

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“…Drug-response variability could be influenced by many factors which are derived from the patients, disease and drug itself [1,2]. Many studies presented that genetic variation could be used as predictor of drug-response variability predictor [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Knowledge, Awareness and Attitude of Pharmacists toward Pharmacogenetic Practice: Perspective of Community and Hospital in Yogyakarta, Indonesia

Perwitasari¹,

Sl²,

Bp³

et al. 2017

J Community Med Health Educ

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Objectives: This study is aimed; to assess the knowledge, awareness and attitude of pharmacists in the community and hospital settings towards pharmacogenetic, to understand the differences of knowledge, awareness and attitude between community and hospital settings and to understand the factors predict the knowledge, awareness and attitude of the pharmacists. Methods:We conducted a cross-sectional study over 60 community pharmacies and 11 clinics and hospital pharmacies. We recruited 84 hospital pharmacists in the private hospitals and 24 community pharmacists. The questionnaire about knowledge, awareness and attitude of pharmacists towards pharmacogenetic were adopted from previous study. We also collected the data of demographic by interviewing the respondents. Results:Our study finds the significant differences of attitude between community and hospital pharmacists. The scores of knowledge, awareness and attitude in community setting are higher than the score of those in hospital settings. In the hospital setting, only education and CPD which may predict the awareness of pharmacists. In the community setting, characteristics which may predict the knowledge, awareness and attitude are outpatient services, work duration and CPD, respectively (p<0.05). Conclusion:The knowledge and awareness of pharmacists toward pharmacogenetic in Yogyakarta are good. Pharmacists' characteristics that may predict the knowledge, awareness and attitude toward pharmacogenetic are education, internal CPD, work duration, and types of patient's service.

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“…Furthermore, genomic advances have started transforming medical care by facilitating inclusion of genetic variants for diagnosis and treatment. As an illustrative example, the field of pharmacogenomics is built on the promise of delivering precision care based on our understanding of genetic variants and their associated risks [30-32]. To deliver this promise to all individuals, the chasm in ancestral diversity of study participants that have remained less represented in GWAS should be addressed [8].…”

Section: Resultsmentioning

confidence: 99%

Examining How Our Shared Evolutionary History Shapes Future Disease Outcomes

Tekola‐Ayele

Peprah

2017

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Cardiometabolic diseases are major contributors to mortality and morbidity, and their burden displays global and regional disparities. Gene-environment interactions contribute to the pathogenesis of cardiometabolic diseases. Population differences in genetic structure, ancient environmental pressures that shape the human genome, and early life environmental adversities (e.g., in utero conditions) all contribute to observed disparities in global cardiometabolic diseases. The genetic and socio-cultural diversity of global populations presents opportunities for discovering genomic loci that influence cardiometabolic diseases as illustrated by a few genetic, epigenetic, and population-genetic discoveries leading to notable understanding of disease mechanisms. However, African, Latin American and Hispanic, and indigenous peoples represent less than 4% of all genome-wide association study samples analyzed to date. Using examples of recent studies in African populations, we discuss the crucial importance of conducting genomic studies in ancestrally diverse populations to understand disease mechanisms and to prepare fertile ground for future delivery of precise health care to all individuals.

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Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine

Cited by 259 publications

References 173 publications

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

Knowledge, Awareness and Attitude of Pharmacists toward Pharmacogenetic Practice: Perspective of Community and Hospital in Yogyakarta, Indonesia

Examining How Our Shared Evolutionary History Shapes Future Disease Outcomes

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