Dataset Information

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.

ABSTRACT: AIM:Multiple genetic variants have been associated with variation in tacrolimus (TAC) trough concentrations. Unfortunately, additional studies do not confirm these associations, leading one to question if a reported association is accurate and reliable. We attempted to validate 44 published variants associated with TAC trough concentrations. MATERIALS & METHODS:Genotypes of the variants in our cohort of 1923 kidney allograft recipients were associated with TAC trough concentrations. RESULTS:Only variants in CYP3A4 and CYP3A5 were significantly associated with variation in TAC trough concentrations in our validation. CONCLUSION:There is no evidence that common variants outside the CYP3A4 and CYP3A5 loci are associated with variation in TAC trough concentrations. In the future rare variants may be important and identified using DNA sequencing.

SUBMITTER: Oetting WS

PROVIDER: S-EPMC6021962 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.

Oetting William S WS Wu Baolin B Schladt David P DP Guan Weihua W Remmel Rory P RP Dorr Casey C Mannon Roslyn B RB Matas Arthur J AJ Israni Ajay K AK Jacobson Pamala A PA

Pharmacogenomics 20180110 3

<h4>Aim</h4>Multiple genetic variants have been associated with variation in tacrolimus (TAC) trough concentrations. Unfortunately, additional studies do not confirm these associations, leading one to question if a reported association is accurate and reliable. We attempted to validate 44 published variants associated with TAC trough concentrations.<h4>Materials & methods</h4>Genotypes of the variants in our cohort of 1923 kidney allograft recipients were associated with TAC trough concentration ...[more]

PMID: 29318894

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Project description:BackgroundCalcineurin inhibitors, including tacrolimus, remain a cornerstone of immunosuppressive therapy after kidney transplantation. However, the therapeutic window is narrow, and nephrotoxic side effects occur with overdose, while the risk of alloimmunization and graft rejection increases with underdose. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allows quantification of tacrolimus in biological samples from patients. This study investigates the feasibility of quantifying tacrolimus in scalp hair from kidney transplant (KT) recipients and correlates hair tacrolimus concentrations with tacrolimus dosage and blood trough levels. The aim was to provide proof-of-principle for hair tacrolimus drug monitoring in KT recipients.MethodSingle-center prospective study between September 9, 2021 and December 4, 2021, including KT recipients under tacrolimus. Minors, patients with active skin or hair diseases, and patients with scalp hair shorter than 4 cm were excluded from participation. Scalp hair was collected from the posterior vertex of patients, cut into segments, and analyzed for tacrolimus by LC-MS/MS. Patients filled out a questionnaire on hair treatments and washing habits. In parallel, tacrolimus trough levels were measured in whole blood and correlated with hair tacrolimus concentrations.ResultsIn total, 39 consenting KT recipients were included, and hair samples were collected at 53 visits. Tacrolimus was detected in 98% of hair samples from patients exposed to the drug. Tacrolimus hair levels and whole blood trough levels were correlated with a beta coefficient of 0.42 (95% CI: -0.22-1.1, p = n.s.). Age and dark hair affected hair tacrolimus measurements, while different tacrolimus formulations (immediate release vs. extended release), hair washes, and permanent coloring did not. Longitudinal measurements in a subgroup of patients indicate that long-term measurement of hair tacrolimus levels is feasible.ConclusionMeasuring tacrolimus in hair is a potentially reliable method to monitor drug exposure in KT patients. Rapid wash-in effects and consistent concentrations over time indicate that tacrolimus is incorporated into the hair matrix, allowing temporal resolution in the analysis of recent exposure and exposure history. This method provides a simple and low-risk alternative to regular blood sampling, sparing patients from frequent hospital visits through the self-collection of hair samples.

Dataset Information

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.

Publications

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.

Similar Datasets

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