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

William S. Oetting; Baolin Wu; David P. Schladt; Weihua Guan; Rory P. Remmel; Casey Dorr; Roslyn B. Mannon; Arthur J. Matas; Ajay K. Israni; Pamala A. Jacobson

doi:10.2217/pgs-2017-0187

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

William S. Oetting, Baolin Wu, David P. Schladt, Weihua Guan, Rory P. Remmel, Casey Dorr, Roslyn B. Mannon, Arthur J. Matas, Ajay K. Israni, Pamala A. Jacobson

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English (US)
Pages (from-to)	175-184
Number of pages	10
Journal	Pharmacogenomics
Volume	19
Issue number	3
DOIs	https://doi.org/10.2217/pgs-2017-0187
State	Published - Feb 2018
Externally published	Yes

Keywords

CYP3A5
GWAS
kidney
tacrolimus
transplantation

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.2217/pgs-2017-0187

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title = "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.",

keywords = "CYP3A5, GWAS, kidney, tacrolimus, transplantation",

author = "Oetting, {William S.} and Baolin Wu and Schladt, {David P.} and Weihua Guan and Remmel, {Rory P.} and Casey Dorr and Mannon, {Roslyn B.} and Matas, {Arthur J.} and Israni, {Ajay K.} and Jacobson, {Pamala A.}",

note = "Publisher Copyright: {\textcopyright} 2018 2018 Future Medicine Ltd.",

year = "2018",

month = feb,

doi = "10.2217/pgs-2017-0187",

language = "English (US)",

volume = "19",

pages = "175--184",

journal = "Pharmacogenomics",

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publisher = "Taylor and Francis Ltd.",

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TY - JOUR

T1 - Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients

AU - Oetting, William S.

AU - Wu, Baolin

AU - Schladt, David P.

AU - Guan, Weihua

AU - Remmel, Rory P.

AU - Dorr, Casey

AU - Mannon, Roslyn B.

AU - Matas, Arthur J.

AU - Israni, Ajay K.

AU - Jacobson, Pamala A.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - CYP3A5

KW - GWAS

KW - kidney

KW - tacrolimus

KW - transplantation

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AN - SCOPUS:85041642709

SN - 1462-2416

VL - 19

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EP - 184

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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