Editing Tacrolimus (section)

===Pharmacogenetics===
The predominant enzyme responsible for metabolism of tacrolimus is [[CYP3A5]]. [[Genetic variation]]s within ''CYP3A5'' that result in changes to the activity of the CYP3A5 protein can affect concentrations of tacrolimus within the body. In particular, individuals who are [[homozygous]] for the G [[allele]] at the [[single nucleotide polymorphism]] (SNP) rs776746 (also known as CYP3A5 *3/*3) have a non-functional CYP3A5 protein. The frequency of the G allele varies worldwide, from 4% in some African populations to 80–90% in Caucasian populations.<ref name="Bains2012">{{cite web| vauthors = Bains RK |title=Molecular diversity and population structure at the CYP3A5 gene in Africa|url=http://discovery.ucl.ac.uk/1356293/7/1356293_R%20Bains%20ELECTRONIC%20VERSION%20thesis%20-%20post%20viva.pdf|publisher=University College London|access-date=13 June 2016}}</ref> Across a large number of studies, individuals homozygous for the G allele have been shown to have higher concentrations of tacrolimus and require lower doses of the drug, as compared to individuals who are not homozygous for the G allele. Achieving target concentrations of tacrolimus is important – if levels are too low, then there is a risk of [[transplant rejection]], if levels are too high, there is a risk of drug toxicities. There is evidence to suggest that dosing patients based on rs776746 [[genotype]] can result in faster and more frequent achievement of target tacrolimus levels. However, there is a lack of consistent evidence as to whether dosing based on rs776746 genotype results in improved clinical outcomes (such as a decreased risk for transplant rejection or drug toxicities), likely because patients taking tacrolimus are subject to [[therapeutic drug monitoring]].<ref>{{cite journal | vauthors = Staatz CE, Tett SE | title = Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation | journal = Clinical Pharmacokinetics | volume = 43 | issue = 10 | pages = 623–653 | date = 2004 | pmid = 15244495 | doi = 10.2165/00003088-200443100-00001 | s2cid = 33877550 }}</ref><ref>{{cite journal | vauthors = Staatz CE, Goodman LK, Tett SE | title = Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I | journal = Clinical Pharmacokinetics | volume = 49 | issue = 3 | pages = 141–175 | date = March 2010 | pmid = 20170205 | doi = 10.2165/11317350-000000000-00000 | s2cid = 28346861 }}</ref><ref>{{cite journal | vauthors = Staatz CE, Goodman LK, Tett SE | title = Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II | journal = Clinical Pharmacokinetics | volume = 49 | issue = 4 | pages = 207–221 | date = April 2010 | pmid = 20214406 | doi = 10.2165/11317550-000000000-00000 | s2cid = 27047235 }}</ref><ref>{{cite journal | vauthors = Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB | title = PharmGKB summary: cyclosporine and tacrolimus pathways | journal = Pharmacogenetics and Genomics | volume = 23 | issue = 10 | pages = 563–585 | date = October 2013 | pmid = 23922006 | pmc = 4119065 | doi = 10.1097/fpc.0b013e328364db84 }}</ref>

Studies have shown that genetic polymorphisms of genes other than CYP3A5, such as NR1I2<ref>{{cite journal | vauthors = Benkali K, Prémaud A, Picard N, Rérolle JP, Toupance O, Hoizey G, Turcant A, Villemain F, Le Meur Y, Marquet P, Rousseau A | title = Tacrolimus population pharmacokinetic-pharmacogenetic analysis and Bayesian estimation in renal transplant recipients | journal = Clinical Pharmacokinetics | volume = 48 | issue = 12 | pages = 805–816 | date = 1 January 2009 | pmid = 19902988 | doi = 10.2165/11318080-000000000-00000 | s2cid = 19900291 }}</ref><ref>{{cite journal | vauthors = Choi Y, Jiang F, An H, Park HJ, Choi JH, Lee H | title = A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform | journal = The Pharmacogenomics Journal | volume = 17 | issue = 1 | pages = 105–106 | date = January 2017 | pmid = 27958377 | doi = 10.1038/tpj.2016.85 | doi-access = free }}</ref> (encoding [[Pregnane X receptor|PXR]]), also significantly influence the pharmacokinetics of tacrolimus.