CYP2D6 polymorphism

Pharmacogenetics: CYP2D6 Genetic Polymorphisms Tabl

The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed. Since CYP2D6 plays a major role in the metabolism of a large number of other drugs, Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinically used drugs The CYP2D6 gene is highly polymorphic, causing absent (poor metabolizers), decreased, normal or increased enzyme activity (extensive and ultrarapid metabolizers). The genetic polymorphism of the CYP2D6 influences plasma concentration of a wide variety of drugs metabolized in the liver by the cytochr CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance Curr Oncol Rep. 2010 Jan;12(1):7-15. doi: 10.1007/s11912-009-0076-5. Authors Michaela J Higgins 1 , Vered Stearns. Affiliation 1 Department of Oncology, Sidney. Polymorphism of CYP2D6 can either increase the rate of drug elimination (ultrametabolizers, leading to faster metabolic clearance potentially resulting in reduced effectiveness and need for higher doses) or decrease drug metabolism (poor metabolizers, which may increase the potential for drug interactions and adverse events) CYP2D6 shows significant pharmacogenetic variation (polymorphism) and is integral in the metabolism of numerous medications, especially psychiatric, narcotic, and cardiac medications. Q3.7 With over 90 documented allelic variants reported, CYP2D6 displays remarkable polymorphism, sometimes with whole gene duplication

CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism. The genotype accounts for normal, reduced, and non-existent CYP2D6 function in subjects CYP2D6 is involved in the metabolism of all of the most commonly available agents, except granisetron, and their efficacy and side effects may therefore be affected by the CYP2D6 polymorphism. Significant interethnic differences in CYP2D6 allele frequencies have been demonstrated from studies across many countries

What Medications are Likely to be Influenced by the

  1. Abstract Cytochrome P450 CYP2D6 is the most extensively characterized polymorphic drug-metabolizing enzyme. A deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait; these subjects (7% of Caucasians, about 1% of Orientals) are classified as poor metabolizers
  2. CYP2D6 highly contributes to drug metabolism. It contains several genetic polymorphisms affecting its enzymatic activity. Metoprolol pharmacokinetics are significantly affected between genotype-inferred phenotypes of CYP2D6, but the impacts on the clinical response of patients to patients have not been summarized. What this study add
  3. Recently, the CYP2D6 oxidation polymorphism has been observed to have an impact on the prevalence of atopic diseases, particularly bronchial asthma and allergic rhinitis. Nearly a 3-fold higher relative risk of development (OR = 2.81) of these diseases was reported in EM subjects and almost 2-fold higher relative risk (OR = 1
  4. The polymorphism of CYP2D6 significantly affects the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The consequences of the polymorphism at ordinary drug..

CYP2D6 is one of the most extensively studied and highly polymorphic among P450s, with more than 100 allelic variants described to date (Frueh et al., 2008; From: Innovative Approaches in Drug Discovery, 201 CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain.METHODS: We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE CYP2D6 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body [ 1 ]. It's found in the liver and the brain [ 2] Read more about CYPs here Abstract: Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme

CYP2D6 Genetic Polymorphisms and Risperidone Pharmacokinetics: A Systematic Review and Meta-analysis Lusi Zhang, Following multiple-dose oral administration, compared with CYP2D6 normal metabolizers, the risperidone dose-adjusted steady-state serum/plasma concentration was 2.35-fold higher in intermediate metabolizers (95% confidence. CYP2D6 is one of the most polymorphic of the cytochrome P450 enzymes. Genetic differences in this enzyme have been reported in whites, blacks, and Asians. However, there is very little information about polymorphisms of this enzyme in Mexican Americans. The objectives of the present study were to as The gene encoding CYP2D6 exhibits high polymorphism, and allelic variants are considered to influence the metabolic pathway of antipsychotics [ 8 ]. The main active metabolite of risperidone is 9-hydroxyrisperidone (9-OH-RIS), which exhibits similar pharmacological actions to risperidone [ 9 ]

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6

  1. CYP2D6 is polymorphically distributed and is responsible for the metabolism of several clinically important drugs. It is also related to several pathophysiological conditions
  2. istration (FDA), and is updated regularly
  3. al oxidases of the mixed function oxidases system, metabolize more than 70% of all clinically approved drugs. The highly polymorphic CYP2D6 isoform metabolizes more than 25% of most common drugs, and the phenotypes of the 70-plus allelic variants range from compromised to excessive enzymatic activity
  4. Additionally, CYP2D6 polymorphisms (* 10, * 5) affect the pharmacokinetic parameters of other atypical antipsychotic drugs, such as risperidone 8 and aripiprazole 9
  5. Wu X., Yuan L., Zuo J., Lv J., et al. The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects. Eur J Clin Pharmacol. 2014; 70 (1):57-63. [PubMed: 24077935
  6. CYP-2D6 polymorphism is of particular importance as to whether patients are able to receive the expected analgesic effect from all of the most commonly prescribed oral opioids (e.g., codeine, hydrocodone (Vicodin®), oxycodone (Per-cocet®), tramadol (Ultram®). 8-10 This is because all of these agents are pro-drugs that need to be metabolized.
  7. Translational Relevance. Although many investigations on tamoxifen pharmacogenomics have been performed, there are still inconsistencies with regard to the association results between efficacy of tamoxifen and genetic polymorphism of CYP2D6, which is the rate-limiting enzyme responsible for the metabolism of tamoxifen to its active metabolite, endoxifen

CYP2D6 polymorphism is associated with variability in drug response, endogenous metabolism (that is, serotonin), personality, neurocognition and psychopathology. The relationship between CYP2D6. CYP2D6*10 polymorphism and the enantioselective O-desmethylation of S-(+)- and R-(-)-venlafaxine in Japanese psychiatric patients Taro Sasaki, Department of Psychiatry, Dokkyo Medical University School of Medicine, Shimotsuga, Japan. Search for more papers by this author The new atypical antidepressant duloxetine is a potent inhibitor of CYP2D6 in vivo and a CYP2D6 substrate in vivo. 43 It therefore seems probable that CYP2D6 genetic polymorphisms have a major.

Frontiers | Long-Distance Phasing of a Tentative “Enhancer

CYP2D6 polymorphism can affect: A) drug efficacy. B) drug toxicity. C) drug interaction potential. D) drug delivery. E) a, b, and c. 11. Which of the following CYP2D6 alleles are associated with reduced or absent CYP2D6 activity? A) CYP2D6*4: B) CYP2D6*5: C) CYP2D6*10: D) CYP2D6*17: E) All the above: 12 The G-3113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in Chinese population. Clin Pharmacol Ther 2005;78:249-59. PubMed. Pavanello S, Pulliero A, Lupi S et al. Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers

Objective. The aim of this study is to evaluate the association of genetic polymorphisms in Cytochrome P450 2D6(CYP2D6) and the change in VEGF levels with the response to propranolol in patients with Infantile hemangiomas (IH). Methods. IH patients who underwent over six months of propranolol therapy and received oral propranolol only were enrolled The cytochrome P450 2D6 (CYP2D6) is an enzyme known to metabolize a variety of xenobiotics and drugs. Inter‐individual variation in the metabolic capacity of this enzyme has been extensively studied and associations with genotype have been established. Genetic polymorphisms have been grouped as nonfunctional, reduced function, functional, and. CYP2D6∗6 (null function, splice aberration) occurs in one in four Caucasians and is the major cause of CYP2D6 poor metabolism. In Asians, CYP2D6∗10 (decreased activity, nonsynonymous polymorphism) and CYP2D6∗41 (decrease Allelic variation at the CYP2D6 gene has been suggested to be associated with CNS disorders, including Parkinson's disease and Lewy body dementia. In order to elucidate whether a relationship exists between CYP2D6 polymorphism and the risk of developing Alzheimer's disease (AD), CYP2D6 allele and genotype frequencies have been evaluated in 94 patients from Southern Italy (29 men and 65 women. Background: CYP2D6 is a xenobiotic metabolizing enzyme , belongs to CYP450 enzyme family. It metabolizes 20-25% of all the drugs. Polymorphisms in these genes will lead to inter individual.

CYP2D6 polymorphism created new interest in the role of pharmacogenetics in clinical pharmacology2. Genetic polymorphism has been linked to three classes of phenotypes based on the extent of dru Therefore, polymorphism of the CYP enzyme system is an essential focus in various pharmacogenetic studies. CYP constitutes a superfamily of haem-containing mono-oxygenases involved in the metabolism of structurally diverse endogenous substrates and xenobiotics ons. Using a sample of CYP2D6 duplication-negative ultrarapid metabolizer subjects and selected control subjects with extensive metabolism, we examined parts of the CYP2D7 pseudogene, and the promoter region and 5′-coding sequence of CYP2D6 for polymorphisms possibly associated with the ultrarapid metabolizer phenotype. In an initial screening of 17 subjects (13 ultrarapid metabolizers and. • Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. • For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions

The analysis of CYP2D6 clinical relevant polymorphisms revealed that 4 patients, each affected by a diagnosis of BD, resulted IMs. Although the limited number of patients, we can confirm that CYP2D6*4 was the most common variant of nonfunctional allele (3/5 of our patients), leading to the poor metabolizer (PM) phenotype in Caucasians. [45 Objective: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6 *4 allele (poor metabolizer phenotype) is associated with earlier age at onset. Methods: Five hundred seventy-six patients with PD and 247 subjects. CYP2D6 is one of the most widely investigated CYPs in relation to its genetic polymorphisms. 7,8 To date, more than 100 allelic variants have been reported for CYP2D6. 9 A combination of polymorphisms, including single nucleotide polymorphisms, duplications, insertions/deletions, and/or gene conversions has been reported to cause either. This study analyzes which people have Cyp2d6 polymorphism with Glipizide and Ibrance. It is created by eHealthMe based on reports from the FDA, and is updated regularly. With medical big data and AI algorithms, eHealthMe enables everyone to run phase IV clinical trial to detect adverse drug outcomes and monitor effectiveness Background: Venlafaxine (V) is a mixed serotonin and noradrenaline reuptake inhibitor used as a first‐line treatment of depressive disorders. It is metabolized primarily by the highly polymorphic cytochrome P450 (CYP) enzyme CYP2D6 to yield a pharmacologically active metabolite, O‐desmethylvenlafaxine (ODV), and to a lesser extent by CYP3A4, to yield N‐desmethylvenlafaxine (NDV)

This study analyzes which people have Cyp2d6 polymorphism with Tresiba and Ondansetron. It is created by eHealthMe based on reports from the FDA, and is updated regularly. With medical big data and AI algorithms, eHealthMe enables everyone to run phase IV clinical trial to detect adverse drug outcomes and monitor effectiveness Subjects. To study the effects of genetic polymorphism of CYP2D6 on pharmacokinetics of metoclopramide, forty-five healthy Korean volunteers were recruited. Each subject provided both verbal and written informed consent before study, and was genotyped for CYP2D6 (CYP2D6*1, *2, *5, *10 and *X × N).Genomic DNA was isolated from peripheral blood leukocytes using the Wizard® Genomic DNA. Objective: To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 ( CYP2D6 ) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). Methods: This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke. This study analyzes which people have Cyp2d6 polymorphism with Phytomenadione and Magnesium. It is created by eHealthMe based on reports from the FDA, and is updated regularly. With medical big data and AI algorithms, eHealthMe enables everyone to run phase IV clinical trial to detect adverse drug outcomes and monitor effectiveness Polymorphisms of the gene for cytochrome P450 2D6 (CYP2D6) influence the rate of elimination of CYP2D6 substrates, which represent approximately 20% of commonly prescribed therapeutic drugs. CYP2D6 substrates include antipsychotic drugs (haloperidol and risperidone), antiarrhythmic agent

The effect of drug-drug interactions (DDIs) and genetic polymorphism of CYP2D6 on the prediction of the metabolic phenotype of CYP2D6 enzyme. To explain the genotype-phenotype shift (phenocopying) due to the DDI effect, we can picture genotypes as a five-step ladder where the top step represents the ultrarapid metabolizer (gUM) and the. Cytochrome P450 (CYP) enzymes such as CYP2D6 are involved in metabolism of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), which often are a first-line choice for patients with major depressive disorder (MDD). 1,2 CYP2D6 is a highly polymorphic gene with 75 allelic variants (CYP2D6*1 to *75) and >30 additional. CYP2D6 polymorphism in patients treated with venlafaxine 499. take inhibitors and angiotensin converting. enzyme inhibitors are reported to be responsible. for a syndrome of inappropriate. The impact of CYP2D6 polymorphism on treatment outcome was tested at the metabolizer phenotype, diplotype and haplotype levels. Results: CYP2D6 polymorphism was significantly associated with opioid treatment outcome (Omnibus P=0.018, for both global haplotype and diplotype distribution test) Polymorphisms in genes encoding for CYP450 enzymes can alter the expression and functional activity of the protein products [].More than 100 allelic variations of CYP2D6 have been described [] and might explain in part the observed interpatient variability in the concentrations of tamoxifen and its metabolites.The wild-type allele is designated CYP2D6*1

This polymorphism is in particular translated into risk differences concerning drugs metabolized by the highly polymorphic enzymes CYP2C9, CYP2C19, and CYP2D6, whereas CYP enzymes active in procarcinogen activation are relatively well conserved without important functional polymorphisms Study Design: Clinically actionable polymorphisms in CYP2D6 (cytochrome p450 2D6) and OPRM1 (μ1 opioid receptor), the most important gene coding, respectively, for a metabolizing enzyme and receptor for opioids are reviewed, and functional effects described The table below is a summary of the main genetic polymorphisms (or variations) of cytochrome P450 (CYP) 3A4 and if known, the populations primarily affected, the specific genetic mutation, and the impact of that mutation on enzyme activity.1-14 Compared to other CYP enzymes involved in drug metabolism, it is well known that a large portion of. This study analyzes which people have Cyp2d6 polymorphism with Exforge and Coq10. It is created by eHealthMe based on reports from the FDA, and is updated regularly. With medical big data and AI algorithms, eHealthMe enables everyone to run phase IV clinical trial to detect adverse drug outcomes and monitor effectiveness The polymorphisms of CYP2D6 and CYP2C19 are relatively well known, and more than 80 mutations of the CYP2D6 gene and about 15 mutations of the CYP2C19 gene have been described [].More than 75 drugs are metabolized by CYP2D6, including antidepressants, selective serotonin reuptake inhibitors and opioids [].The CYP2C19 metabolizes more than 25 drugs including proton pump inhibitors and some.

CYP2D6 Polymorphism: Implications for Antipsychotic Drug

The present study looked for two polymorphisms (m1 and m2) in the CYP1A1, CYP2D6*4 genes and deletions of the glutathione S‐transferases (GSTM1 and GSTT1) in 118 paediatric ALL patients and 118 age matched control children. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to study gene. Conversely, no significant influence was found among CYP2D6 polymorphisms, plasma concentrations of 9-hydroxyrisperidone, and the total active moiety. Conclusions: This is the first study to investigate the effects of CYP2D6 genetic polymorphisms on the plasma concentrations of risperidone in Thai children with ASD. The findings indicate that. Discussion. Genetic polymorphism of CYP2D6 in Iranian breast cancer patients treated with tamoxifen was the focus of the present study. There has been numerous studies performed on this topic with conflicting results, particularly when examining the clinical impact of this variation on patient outcome and response to hormonal therapy (23,27,28).Of the four CYP2D6 alleles evaluated in the. Candiotti KA, Zonggi Y, Rodriguez V, et al. The impact of CYP2D6 genetic polymorphisms on postoperative morphine consumption. Pain Med. 2009;10(5):799-805. Mikus G, Weiss J. Influence of CYP2D6 genetics on opioid kinetics, metabolism and response. Current Pharmacogenomics. 2005;3(1):43-52 Tolterodine is metabolized to an active 5-hydroxymethyl tolterodine (5-HMT) by CYP2D6. This study investigated the relationship between CYP2D6 genotypes and pharmacokinetics of tolterodine and its active metabolite in healthy Korean subjects. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10.

CYP2D6 polymorphisms and tamoxifen metabolism: clinical

CYP2D6, a highly polymorphic enzyme, constitutes only a small percentage of the CYP450 proteins (<2%); however, it is involved in the metabolism of ~25% of clinical therapeutic drugs, including antidepressants, antitussives, β-adrenergic antagonists, antipsychotic agents, opioid drugs, and antiarrhythmic agents. 7-11 CYP2D6 has extensive genetic polymorphisms with at least 105 allelic. An effect of CYP2D6 polymorphism on hydrocodone metabolite production has been demonstrated. However, evidence suggests that analgesic efficacy of hydrocodone is not affected by metabolism via CYP2D6. Effect of CYP2D6 polymorphisms on hydrocodone toxicity has also been reported (Table 2). Madadi et al. reported a case of fatal opioid toxicity. CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study Ishani Wickramage,1 Kamani Hemamala Tennekoon,1 Merenchi Arachchige Yasantha Ariyaratne,2 Asanka Sudeshini Hewage,1 Tharmini Sundralingam,1 1Institute of Biochemistry, Molecular Biology and Biotechnology (IBMBB), University of Colombo, Colombo, Sri Lanka; 2National Cancer Institute. The Human Genome Project has identified 57 human CYPs; however, 90% of drugs are metabolized by six of those enzymes, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. 12 Over 2,000 allelic variations have been observed in these CYP enzymes, most of which occur due to SNPs. 13 Genetic polymorphism in CYP enzymes typically contributes to a. Understanding the genetics of CYP2D6 is of utmost importance from a clinical standpoint because the enzyme is responsible for metabolizing >30% of drugs belonging to different therapeutic classes. Unlike polymorphisms in other cytochromes, polymorphisms in CYP2D6 result not only from single-nucleotide polymorphisms but also from insertion/deletions of nucleotide bases (indels), in addition to.

Genetic polymorphism of cytochrome P450 enzymes in Asian

Genetic polymorphisms cause large inter-individual variability in CYP2D6 enzyme activity and are currently used as biomarker to predict CYP2D6 metabolizer phenotype. Previously, we had identified a region 115 kb downstream of CYP2D6 as enhancer for CYP2D6 , containing two completely linked single nucleotide polymorphisms (SNPs), rs133333 and. CYP2D6 is a key enzyme for the generation of 4-hydroxytamoxifen and endoxifen. 6 Several groups including ours have clarified that loss or decrease of CYP2D6 function by genetic polymorphisms is associated with poorer clinical outcome of tamoxifen treatment in different populations. 7-10 Although genetic polymorphisms in CYP2D6 are one of the.

CYP2D6 - an overview ScienceDirect Topic

Third, in respect to the present analysis in which the main 16 clinical relevant CYP2D6 polymorphisms were investigated, in the previous studies only a limited number of CYP2D6 alleles were included. The missing identification of a number of CYP2D6 variants associated to a reduced (non null) enzyme activity introduced a bias in the EM group. Keywords: CYP2D6, Polymorphisms, Risperidone, Plasma concentration, Therapeutic effect Background Risperidone, an atypical antipsychotic, is widely used for the treatment of psychiatric problems and is associated with better compliance and reduced incidence of advers Both CYP2D6*5 and *10 polymorphism altered the pharmacokinetics of nebivolol in healthy Chinese volunteers. Further studies are required to investigate the effects of these single-nucleotide polymorphisms on the pharmacokinetics, pharmacodynamics and toxicity of nebivolol CYP2D6 Of all CYP enzymes, the highly genetically polymorphic enzyme debrisoquine-4-hydroxy­ lase, or CYP2D6, has been the most extensively studied. CYP2D6 is involved in the oxidative metabolism of more than 40 widely prescribed drugs (Table 2). The gene that codes for the CYP2D6 enzyme has been localized to chromo

Effects of the CYP2D6*10 C188T Polymorphism on Pharmacokinetics of M 1. There were three studies that reported the effect of CYP2D6*10 C188T polymorphism on the pharmacokinetic parameters (including AUC 0-∞ and C max) of M1 [3, 24, 25]. However, one study lacked the data of subjects carrying CT genotype The wikipedia article on CYP2D6 is a good resource to learn about this gene, and includes a large table of the drugs known to be metabolized by the CYP2D6 protein. In fact, almost 25% of all drugs are metabolized by CYP2D6, including dextromethorphan (a key ingredient in products such as Nyquil), beta-blockers, antiarrhythmics, and antidepressants.. CYP2D6 polymorphisms have been demonstrated to affect the enzymatic activity of the expressed protein, 26,27 which has been shown to have a major impact on the pharmacokinetics of the β-blocker metoprolol. 8,28 This has led to questions about the effects of these kinetic differences on drug adverse effects and efficacy. 21,29 In the present. CYP2D6 is a member of the cytochrome P450 family of enzymes involved in the oxidative metabolism of drugs. CYP2D6 is among the most promiscuous of these enzymes, involved in the metabolism of approximately 20% of drugs in clinical use, and displays large individual-to-individual variability in activity due to genetic polymorphisms Risperidone is mainly metabolized by cytochrome P450 (CYP) 2D6 in the liver. The gene encoding CYP2D6 is highly polymorphic. The average steady-state plasma concentration of risperidone active moiety is higher in the CYP2D6 intermediate metabolizers (IMs) compared with that in the extensive metabolizers (EMs). An association between drug-induced extrapyramidal symptoms scale (DIEPSS) score and.

Genes | Free Full-Text | Genetic Polymorphisms and InInnovative Epilepsy Therapies for the 21st Century - Part 3PharmacogeneticsThe CYP2C19 Intron 2 Branch Point SNP is the Ancestral[Full text] The frequency of CYP2C19 genetic polymorphisms

Ozawa S, Soyama A, Saeki M, et al. Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1. Drug Metab Pharmacokinet . 2004;19(2):83-95 This study aimed to investigate genetic polymorphisms of CYP2D6 among healthy Uygur individuals. Genetic polymorphisms of CYP2D6 could greatly affect CYP2D6 activity and lead to differences among individuals in drug efficacy or side effects. To investigate genetic polymorphisms of CYP2D6 in the Uygur population, we directly sequenced the whole gene in 96 unrelated, healthy Uygur volunteers. CYP2D6 polymorphism of drug metabolism represents an important source of interindividual and interethnic variation in drug response. Since this polymorphism has not been studied in an Iranian. Pharmacogenetics: CYP2C9 Genetic Polymorphisms. Note: C = cystine, D = aspartate, E = glutamate, I = isoleucine, L = leucine, R = arginine, W = tryptophan; letters in (parenthesis) represent the single nucleotides that make up the DNA sequence and codons to code for an amino acid (A = adenine, C = cytosine, G = guanine, T = thymine) The CYP2D6 polymorphisms were genotyped using the INFINITI™ CYP450 2D6I assay, while the polymorphisms in CYP3A5, CYP2C9 and CYP2C19 were determined via direct sequencing. RESULTS The polymorphisms, CYP2D6*5 and *10, were significantly associated with lower endoxifen and higher N-desmethyltamoxifen (NDM) concentrations