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Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients

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Canet, LM, Sánchez-Maldonado, JM, Cáliz, R, Ramos, AR, Lupiañez, CB, Canhão, H, Martínez-Bueno, M, Escudero, A, Segura-Catena, J, Sorensen, SB, Hetland, ML, Soto-Pino, MJ, Ferrer, MA, García, A, Glintborg, B, Filipescu, I, Pérez-Pampin, E, González-Utrilla, A, Nevot, MÁL, Conesa-Zamora, P, Broeder, AD, De Vita, S, Jacobsen, SEH, Collantes-Estevez, E, Quartuccio, L, Canzian, F, Fonseca, JE, Coenen, MJH, Andersen, V & Sainz, J 2019, 'Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients' The pharmacogenomics journal, vol. 19, no. 1, pp. 83-96. https://doi.org/10.1038/s41397-018-0057-x

APA

CBE

Canet LM, Sánchez-Maldonado JM, Cáliz R, Ramos AR, Lupiañez CB, Canhão H, Martínez-Bueno M, Escudero A, Segura-Catena J, Sorensen SB, Hetland ML, Soto-Pino MJ, Ferrer MA, García A, Glintborg B, Filipescu I, Pérez-Pampin E, González-Utrilla A, Nevot MÁL, Conesa-Zamora P, Broeder AD, De Vita S, Jacobsen SEH, Collantes-Estevez E, Quartuccio L, Canzian F, Fonseca JE, Coenen MJH, Andersen V, Sainz J. 2019. Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients. The pharmacogenomics journal. 19(1):83-96. https://doi.org/10.1038/s41397-018-0057-x

MLA

Vancouver

Author

Canet, Luz M ; Sánchez-Maldonado, Jose M ; Cáliz, Rafael ; Ramos, Ana Rodríguez ; Lupiañez, Carmen B ; Canhão, Helena ; Martínez-Bueno, Manuel ; Escudero, Alejandro ; Segura-Catena, Juana ; Sorensen, Signe B ; Hetland, Merete L ; Soto-Pino, María José ; Ferrer, Miguel A ; García, Antonio ; Glintborg, Bente ; Filipescu, Ileana ; Pérez-Pampin, Eva ; González-Utrilla, Alfonso ; Nevot, Miguel Ángel López ; Conesa-Zamora, Pablo ; Broeder, Alfons den ; De Vita, Salvatore ; Jacobsen, Sven Erik Hobe ; Collantes-Estevez, Eduardo ; Quartuccio, Luca ; Canzian, Federico ; Fonseca, João E ; Coenen, Marieke J H ; Andersen, Vibeke ; Sainz, Juan. / Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients. In: The pharmacogenomics journal. 2019 ; Vol. 19, No. 1. pp. 83-96.

Bibtex

@article{ffe979506f784aeabc6ebb96fb2fcc0a,
title = "Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients",
abstract = "The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries. Although none of the selected variants had a relevant role in modulating RA risk, the meta-analysis of the linear regression data with those from the DREAM and DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti-TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype analysis also showed that the ESR2GGG haplotype significantly associated with a reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a ROC curve analysis confirmed that a model built with eight steroid hormone-related variants significantly improved the ability to predict drug response compared with the reference model including demographic and clinical variables (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 × 10-6). These data together with those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 × 10-6 to P = 2.0 × 10-35), and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs, suggest that steroid hormone-related genes may have a role in determining the response to anti-TNF drugs.KEY POINTS• Polymorphisms within the CYP3A4 and CYP2C9 loci correlate with changes in DAS28 after treatment with anti-TNF drugs.• A haplotype including eQTL SNPs within the ESR2 gene associates with better response to anti-TNF drugs.• A genetic model built with eight steroid hormone-related variants significantly improved the ability to predict drug response.",
keywords = "Antirheumatic Agents/therapeutic use, Arthritis, Rheumatoid/drug therapy, Case-Control Studies, Cytochrome P-450 CYP2C9/genetics, Cytochrome P-450 CYP3A/genetics, Estrogen Receptor beta/genetics, Female, Gonadal Steroid Hormones/genetics, Haplotypes/genetics, Humans, Male, Metabolic Detoxication, Phase I/genetics, Polymorphism, Single Nucleotide/genetics, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Ubiquitin-Protein Ligases/genetics",
author = "Canet, {Luz M} and S{\'a}nchez-Maldonado, {Jose M} and Rafael C{\'a}liz and Ramos, {Ana Rodr{\'i}guez} and Lupia{\~n}ez, {Carmen B} and Helena Canh{\~a}o and Manuel Mart{\'i}nez-Bueno and Alejandro Escudero and Juana Segura-Catena and Sorensen, {Signe B} and Hetland, {Merete L} and Soto-Pino, {Mar{\'i}a Jos{\'e}} and Ferrer, {Miguel A} and Antonio Garc{\'i}a and Bente Glintborg and Ileana Filipescu and Eva P{\'e}rez-Pampin and Alfonso Gonz{\'a}lez-Utrilla and Nevot, {Miguel {\'A}ngel L{\'o}pez} and Pablo Conesa-Zamora and Broeder, {Alfons den} and {De Vita}, Salvatore and Jacobsen, {Sven Erik Hobe} and Eduardo Collantes-Estevez and Luca Quartuccio and Federico Canzian and Fonseca, {Jo{\~a}o E} and Coenen, {Marieke J H} and Vibeke Andersen and Juan Sainz",
note = "COPECARE",
year = "2019",
month = "2",
doi = "10.1038/s41397-018-0057-x",
language = "English",
volume = "19",
pages = "83--96",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients

AU - Canet, Luz M

AU - Sánchez-Maldonado, Jose M

AU - Cáliz, Rafael

AU - Ramos, Ana Rodríguez

AU - Lupiañez, Carmen B

AU - Canhão, Helena

AU - Martínez-Bueno, Manuel

AU - Escudero, Alejandro

AU - Segura-Catena, Juana

AU - Sorensen, Signe B

AU - Hetland, Merete L

AU - Soto-Pino, María José

AU - Ferrer, Miguel A

AU - García, Antonio

AU - Glintborg, Bente

AU - Filipescu, Ileana

AU - Pérez-Pampin, Eva

AU - González-Utrilla, Alfonso

AU - Nevot, Miguel Ángel López

AU - Conesa-Zamora, Pablo

AU - Broeder, Alfons den

AU - De Vita, Salvatore

AU - Jacobsen, Sven Erik Hobe

AU - Collantes-Estevez, Eduardo

AU - Quartuccio, Luca

AU - Canzian, Federico

AU - Fonseca, João E

AU - Coenen, Marieke J H

AU - Andersen, Vibeke

AU - Sainz, Juan

N1 - COPECARE

PY - 2019/2

Y1 - 2019/2

N2 - The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries. Although none of the selected variants had a relevant role in modulating RA risk, the meta-analysis of the linear regression data with those from the DREAM and DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti-TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype analysis also showed that the ESR2GGG haplotype significantly associated with a reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a ROC curve analysis confirmed that a model built with eight steroid hormone-related variants significantly improved the ability to predict drug response compared with the reference model including demographic and clinical variables (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 × 10-6). These data together with those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 × 10-6 to P = 2.0 × 10-35), and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs, suggest that steroid hormone-related genes may have a role in determining the response to anti-TNF drugs.KEY POINTS• Polymorphisms within the CYP3A4 and CYP2C9 loci correlate with changes in DAS28 after treatment with anti-TNF drugs.• A haplotype including eQTL SNPs within the ESR2 gene associates with better response to anti-TNF drugs.• A genetic model built with eight steroid hormone-related variants significantly improved the ability to predict drug response.

AB - The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries. Although none of the selected variants had a relevant role in modulating RA risk, the meta-analysis of the linear regression data with those from the DREAM and DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti-TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype analysis also showed that the ESR2GGG haplotype significantly associated with a reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a ROC curve analysis confirmed that a model built with eight steroid hormone-related variants significantly improved the ability to predict drug response compared with the reference model including demographic and clinical variables (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 × 10-6). These data together with those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 × 10-6 to P = 2.0 × 10-35), and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs, suggest that steroid hormone-related genes may have a role in determining the response to anti-TNF drugs.KEY POINTS• Polymorphisms within the CYP3A4 and CYP2C9 loci correlate with changes in DAS28 after treatment with anti-TNF drugs.• A haplotype including eQTL SNPs within the ESR2 gene associates with better response to anti-TNF drugs.• A genetic model built with eight steroid hormone-related variants significantly improved the ability to predict drug response.

KW - Antirheumatic Agents/therapeutic use

KW - Arthritis, Rheumatoid/drug therapy

KW - Case-Control Studies

KW - Cytochrome P-450 CYP2C9/genetics

KW - Cytochrome P-450 CYP3A/genetics

KW - Estrogen Receptor beta/genetics

KW - Female

KW - Gonadal Steroid Hormones/genetics

KW - Haplotypes/genetics

KW - Humans

KW - Male

KW - Metabolic Detoxication, Phase I/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors

KW - Ubiquitin-Protein Ligases/genetics

UR - http://www.scopus.com/inward/record.url?scp=85054508665&partnerID=8YFLogxK

U2 - 10.1038/s41397-018-0057-x

DO - 10.1038/s41397-018-0057-x

M3 - Journal article

VL - 19

SP - 83

EP - 96

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 1

ER -

ID: 56070256