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.

• Authors: Patrizia Russo, Carlo Tomino, Alessia Santoro, Giulia Prinzi, Stefania Proietti, Aliaksei Kisialiou, Vittorio Cardaci, Massimo Fini, Mauro Magnani, Francesco Collacchi, Mauro Provinciali, Robertina Giacconi, Stefano Bonassi, Marco Malavolta
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 8 (Apr 24 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31022961 (Publication Type: Journal Article)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Adrenal Cortex Hormones
• GLCCI1 protein, human
• NR3C1 protein, human
• Receptors, Glucocorticoid
• Tacrolimus Binding Proteins
• tacrolimus binding protein 5

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Administration, Inhalation
• Adrenal Cortex Hormones (administration & dosage, therapeutic use)
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Pulmonary Disease, Chronic Obstructive (drug therapy, genetics)
• Receptors, Glucocorticoid (genetics)
• Tacrolimus Binding Proteins (genetics)
• Treatment Outcome