Influence of <i><scp>ABCC</scp>2, <scp>CYP</scp>2C8</i>, and <i><scp>CYP</scp>2J2</i> Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

Genvigir, Fabiana Dalla Vecchia; Nishikawa, Alvaro Mitsunori; Felipe, Cláudia Rosso; Tedesco‐Silva, Hélio; Oliveira, Nara Rejane Cruz de; Salazar, Antony Brayan Campos; Medina‐Pestana, José Osmar; Doi, Sonia Q.; Hirata, Mario H.; Hirata, Rosário Dominguez Crespo

doi:10.1002/phar.1928

Cited by 33 publications

(21 citation statements)

References 36 publications

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“…The CC genotype of another SNP (rs2280275) has been suggested to be a genetic marker for risk of essential hypertension in an Uygur population but not in a Han population [ 112 ]. The CYP2J2*7 SNP has also been reported to affect the renal function and the risk of adverse events associated with tacrolimus and mycophenolate sodium in kidney transplant patients in Brazil [ 113 ]. Although not conclusive, CYP2J2 genetic variation may reduce EET levels, which could potentially lead to hypertension.…”

Section: Protective Role Of Cyp2j2 In the Kidneymentioning

confidence: 99%

Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes

Aliwarga

Evangelista

Sotoodehnia

et al. 2018

IJMS

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Cytochrome P450 2J2 (CYP2J2) is a known arachidonic acid (AA) epoxygenase that mediates the formation of four bioactive regioisomers of cis-epoxyeicosatrienoic acids (EETs). Although its expression in the liver is low, CYP2J2 is mainly observed in extrahepatic tissues, including the small intestine, pancreas, lung, and heart. Changes in CYP2J2 levels or activity by xenobiotics, disease states, or polymorphisms are proposed to lead to various organ dysfunctions. Several studies have investigated the regulation of CYP2J2 and EET formation in various cell lines and have demonstrated that such regulation is tissue-dependent. In addition, studies linking CYP2J2 polymorphisms to the risk of developing cardiovascular disease (CVD) yielded contradictory results. This review will focus on the mechanisms of regulation of CYP2J2 by inducers, inhibitors, and oxidative stress modeling certain disease states in various cell lines and tissues. The implication of CYP2J2 expression, polymorphisms, activity and, as a result, EET levels in the pathophysiology of diabetes and CVD will also be discussed.

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Section: Protective Role Of Cyp2j2 In the Kidneymentioning

confidence: 99%

Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes

Aliwarga

Evangelista

Sotoodehnia

et al. 2018

IJMS

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“…On the other hand, many genetic polymorphisms within Phase II drug metabolizing genes were defined as VIP variants and related to different diseases important to pharmacogenetics. Within UGT1A1 gene the rs8175347 and rs10929302 (AA) have been implicated in toxicity, increased risk of diarrhea and neutropenia when treated with irinotecan in people with colorectal neoplasms [29,30].…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms of Pharmacogenes among the Genetically Isolated Circassian Subpopulation from Jordan

AL-Eitan

Rababa'h

Hakooz

et al. 2020

JPM

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Several genetic variants have been identified that cause variation among different populations and even within individuals of a similar descent. This leads to interindividual variations in the optimal dose of the drug that is required to sustain the treatment efficiency. In this study, 56 single nucleotide polymorphisms (SNPs) within several pharmacogenes were analyzed in 128 unrelated subjects from a genetically isolated group of Circassian people living in Jordan. We also compared these variant distributions to other ethnic groups that are available at two databases (Genome 1000 and eXAC). Our results revealed that the distribution of allele frequencies within genes among Circassians in Jordan showed similarities and disparities when compared to other populations. This study provides a powerful base for clinically relevant SNPs to enhance medical research and future pharmacogenomic studies. Rare variants detected in isolated populations can significantly guide to novel loci involved in the development of clinically relevant traits.

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“…Capron et al . found that patients with the ABCB1 3435T or the 2677T/A allele had 1.3-fold higher Tac concentrations within circulating lymphocytes compared with wild-type homozygotes [ 107 ]. These studies provide evidences that ABCB1 3435C>T and 2677G>T/A affect Tac distribution into lymphocytes with the variant alleles which are associated with an increased pharmacodynamic effect of Tac.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation

Liu

Zhang

et al. 2018

CDM

129

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Background: Tacrolimus (Tac, or FK506), a calcineurin inhibitor (CNI), is the first-line immu-nosuppressant which consists of the footstone as immunosuppressive regimens in kidney transplantation. However, the drug toxicity and the significant differences of pharmacokinetics (PK) and pharmacodynam-ics (PD) among individuals are hidden troubles for clinical application. Recently, emerging evidences of Tac pharmacogenetics (PG) regarding drug absorption, metabolism, disposition, excretion and response are discovered for better understanding of this drug.Method: We reviewed the published articles regarding the Tac PG and its effects on PK and PD in kidney transplantation. In addition, we summarized information on polygenic algorithms.Results: The polymorphism of genes encoding metabolic enzymes and transporters related to Tac were largely investigated, but the results were inconsistent. In addition to CYP3A4, CYP3A5 and P-gp (also known as ABCB1), single nucleotide polymorphisms (SNPs) might also affect the PK and PD parameters of Tac.Conclusion: The correlation between Tac PK, PD and PG is very complex. Although many factors need to be verified, it is envisaged that thorough understanding of PG may assist clinicians to predict the optimal starting dosage, help adjust the maintenance regimen, as well as identify high risk patients for adverse ef-fects or drug inefficacy

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Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

Abstract: The ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.-76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium.

Cited by 33 publications

References 36 publications

Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes

Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes

Genetic Polymorphisms of Pharmacogenes among the Genetically Isolated Circassian Subpopulation from Jordan

Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation

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