PharmGKB summary: very important pharmacogene information for CYP3A5.

The aim of a PharmGKB VIP summary is to provide a simple overview of a gene with respect to drug effects. In some cases, there may be extensive evidence of variants that have known pharmacogenomic relevance, whereas in other cases, the summary may serve to highlight the gaps in knowledge where further study would aid the field. This summary points to the PharmGKB website to provide an interactive version that is linked to annotated publications and to related drugs, diseases, and pathways. The human CYP3A subfamily, CYP3A4, CYP3A5, CYP3A7, and CYP3A43, is one of the most versatile of the biotransformation systems that facilitate the elimination of drugs (37% of the 200 most frequently prescribed drugs in the US [1]). Together, CYP3A4 and CYP3A5 account for ~30% of hepatic cytochrome P450, and approximately half of the medications that are oxidatively metabolized by P450 are CYP3A substrates. Both CYP3A4 and CYP3A5 are expressed in the liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues. The CYP3A5 cDNA sequence was first described independently by Aoyama et al. [2] and Schuetz et al. [3]. The CYP3A5 gene is located on chromosome 7q22.1 along with other CYP3A family members. The gene is on the minus chromosomal strand, consists of nine exons, and encodes a 502-amino-acid protein.

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[2]  T. Aoyama,et al.  Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. , 1989, The Journal of biological chemistry.

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[4]  Ann Daly,et al.  Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression , 2001, Nature Genetics.

[5]  M. Haberl,et al.  The genetic determinants of the CYP3A5 polymorphism. , 2001, Pharmacogenetics.

[6]  E. Schuetz,et al.  Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. , 2002, Molecular pharmacology.

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[8]  F. Behm,et al.  Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies. , 2002, Pharmacogenetics.

[9]  R. V. van Schaik,et al.  CYP3A5 variant allele frequencies in Dutch Caucasians. , 2002, Clinical chemistry.

[10]  Jin‐ding Huang,et al.  Pharmacokinetics of midazolam and 1'-hydroxymidazolam in Chinese with different CYP3A5 genotypes. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[11]  E. Schuetz,et al.  Tacrolimus Dosing in Pediatric Heart Transplant Patients is Related to CYP3A5 and MDR1 Gene Polymorphisms , 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[12]  P. Watkins,et al.  CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. , 2003, Journal of applied physiology.

[13]  R. Kim,et al.  Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. , 2003, Pharmacogenetics.

[14]  Y. Cheung,et al.  CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations , 2003, European Journal of Clinical Pharmacology.

[15]  Ernest Hodgson,et al.  Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups. , 2003, Pharmacogenetics.

[16]  P. Syrris,et al.  The Influence of Pharmacogenetics on the Time to Achieve Target Tacrolimus Concentrations after Kidney Transplantation , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[17]  Yang Dai,et al.  In vitro metabolism of cyclosporine A by human kidney CYP3A5. , 2004, Biochemical pharmacology.

[18]  D. Oh,et al.  Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states , 2004, Clinical pharmacology and therapeutics.

[19]  T. Strandberg,et al.  Lipid-lowering response to statins is affected by CYP3A5 polymorphism. , 2004, Pharmacogenetics.

[20]  A. Telenti,et al.  Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects , 2004, European Journal of Clinical Pharmacology.

[21]  L. Williams,et al.  CYP3A5 Genotype has a Dose‐dependent Effect on ABT‐773 Plasma Levels , 2004, Clinical pharmacology and therapeutics.

[22]  W. Haefeli,et al.  Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics. , 2004, British journal of clinical pharmacology.

[23]  David B. Witonsky,et al.  CYP3A variation and the evolution of salt-sensitivity variants. , 2004, American journal of human genetics.

[24]  Russell A Wilke,et al.  Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage , 2005, Pharmacogenetics and genomics.

[25]  Qi Li,et al.  Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus. , 2005, Transplantation proceedings.

[26]  P. Watkins,et al.  Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5 , 2005, Clinical pharmacology and therapeutics.

[27]  Zhi-Hong Liu,et al.  Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation , 2005, Clinical transplantation.

[28]  P. Beaune,et al.  Cytochrome P450 3A polymorphisms and immunosuppressive drugs. , 2005, Pharmacogenomics.

[29]  D. Holt,et al.  Tacrolimus Pharmacogenetics: The CYP3A5*1 Allele Predicts Low Dose-Normalized Tacrolimus Blood Concentrations in Whites and South Asians , 2005, Transplantation.

[30]  Brian R. Phillips,et al.  CONTRIBUTION OF CYP3A5 TO HEPATIC AND RENAL IFOSFAMIDE N-DECHLOROETHYLATION , 2005, Drug Metabolism and Disposition.

[31]  C. Dandara,et al.  CYP3A5 genotypes and risk of oesophageal cancer in two South African populations. , 2005, Cancer letters.

[32]  J. Flaws,et al.  Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. , 2005, Cancer letters.

[33]  U. Kunzendorf,et al.  CYP3A5 Genotype Markedly Influences the Pharmacokinetics of Tacrolimus and Sirolimus in Kidney Transplant Recipients , 2007, Clinical pharmacology and therapeutics.

[34]  D. Toncheva,et al.  Genotyping of CYP3A5 Polymorphisms among Bulgarian Patients with Sporadic Colorectal Cancer and Controls , 2007, Oncology Research and Treatment.

[35]  M. Schwab,et al.  Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation , 2008, Analytical and bioanalytical chemistry.

[36]  S. Y. Park,et al.  Frequencies of CYP3A5 genotypes and haplotypes in a Korean population , 2008, Journal of clinical pharmacy and therapeutics.

[37]  M. Hirata,et al.  CYP3A53A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[38]  B. Charpentier,et al.  Influence of CYP3A5 genetic polymorphism on tacrolimus daily dose requirements and acute rejection in renal graft recipients. , 2008, Basic & clinical pharmacology & toxicology.

[39]  S. Tsugane,et al.  Genetic polymorphisms in estrogen metabolism and breast cancer risk in case–control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians , 2009, Journal of Human Genetics.

[40]  A. Borobia,et al.  Trough Tacrolimus Concentrations in the First Week After Kidney Transplantation Are Related to Acute Rejection , 2009, Therapeutic drug monitoring.

[41]  Jos H Beijnen,et al.  Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa. , 2009, British journal of clinical pharmacology.

[42]  C. O’Seaghdha,et al.  Higher tacrolimus trough levels on days 2–5 post‐renal transplant are associated with reduced rates of acute rejection , 2009, Clinical transplantation.

[43]  M. Burnier,et al.  CYP3A5 and ABCB1 genes and hypertension. , 2009, Pharmacogenomics.

[44]  M. Hirata,et al.  Statin regulation of CYP3A4 and CYP3A5 expression. , 2009, Pharmacogenomics.

[45]  M. Loriot,et al.  Optimization of Initial Tacrolimus Dose Using Pharmacogenetic Testing , 2010, Clinical pharmacology and therapeutics.

[46]  C. Staatz,et al.  Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part I , 2010, Clinical pharmacokinetics.

[47]  K. Sailaja,et al.  Analysis of CYP3A5*3 and CYP3A5*6 gene polymorphisms in Indian chronic myeloid leukemia patients. , 2010, Asian Pacific journal of cancer prevention : APJCP.

[48]  C. Staatz,et al.  Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part II , 2010, Clinical pharmacokinetics.

[49]  M. Climent,et al.  Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. , 2011, The Lancet. Oncology.

[50]  A. Israni,et al.  Dosing equation for tacrolimus using genetic variants and clinical factors. , 2011, British journal of clinical pharmacology.

[51]  K. Schmiegelow,et al.  The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia , 2011, European journal of haematology.

[52]  S. Hall,et al.  Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia , 2011, Pediatric blood & cancer.

[53]  J. Mi,et al.  Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension , 2011, Hypertension Research.

[54]  C. Adithan,et al.  Genetic polymorphisms of drug‐metabolizing phase I enzymes CYP2E1, CYP2A6 and CYP3A5 in South Indian population , 2012, Fundamental & clinical pharmacology.

[55]  Yoshiro Saito,et al.  Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development. , 2012, Drug metabolism and pharmacokinetics.