FKBP5 rs4713916: A potential genetic predictor of interindividual different response to inhaled corticosteroids in patients with chronic obstructive pulmonary disease in a real-life setting

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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.

Original languageEnglish
Article number2024
JournalInternational Journal of Molecular Sciences
Volume20
Issue number8
DOIs
Publication statusPublished - Apr 2 2019

Fingerprint

corticosteroids
Pulmonary diseases
Chronic Obstructive Pulmonary Disease
Adrenal Cortex Hormones
predictions
glucocorticoids
Genes
genes
Single Nucleotide Polymorphism
Nucleotides
Disease Progression
Polymorphism
Genotype
polymorphism
nucleotides
Lung
lungs
Pharmacogenetics
Glucocorticoid Receptors
expiration

Keywords

  • COPD
  • Inhaled corticosteroid
  • Lung function
  • Rehabilomics
  • Rs37972
  • Rs471396

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{1ad31abb43cc477685de246fa7861186,
title = "FKBP5 rs4713916: A potential genetic predictor of interindividual different response to inhaled corticosteroids in patients with chronic obstructive pulmonary disease in a real-life setting",
abstract = "Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.",
keywords = "COPD, Inhaled corticosteroid, Lung function, Rehabilomics, Rs37972, Rs471396",
author = "Patrizia Russo and Carlo Tomino and Alessia Santoro and Giulia Prinzi and Stefania Proietti and Aliaksei Kisialiou and Vittorio Cardaci and Massimo Fini and Mauro Magnani and Francesco Collacchi and Mauro Provinciali and Robertina Giacconi and Stefano Bonassi and Marco Malavolta",
year = "2019",
month = "4",
day = "2",
doi = "10.3390/ijms20082024",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
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TY - JOUR

T1 - FKBP5 rs4713916

T2 - A potential genetic predictor of interindividual different response to inhaled corticosteroids in patients with chronic obstructive pulmonary disease in a real-life setting

AU - Russo, Patrizia

AU - Tomino, Carlo

AU - Santoro, Alessia

AU - Prinzi, Giulia

AU - Proietti, Stefania

AU - Kisialiou, Aliaksei

AU - Cardaci, Vittorio

AU - Fini, Massimo

AU - Magnani, Mauro

AU - Collacchi, Francesco

AU - Provinciali, Mauro

AU - Giacconi, Robertina

AU - Bonassi, Stefano

AU - Malavolta, Marco

PY - 2019/4/2

Y1 - 2019/4/2

N2 - Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.

AB - Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.

KW - COPD

KW - Inhaled corticosteroid

KW - Lung function

KW - Rehabilomics

KW - Rs37972

KW - Rs471396

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U2 - 10.3390/ijms20082024

DO - 10.3390/ijms20082024

M3 - Article

C2 - 31022961

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VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

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