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Open AccessArticle

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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Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Via di Valcannuta, 247 00166 Rome, Italy
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Scientific Direction, IRCCS San Raffaele Pisana, 0166 Rome, Italy
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Pulmonary Rehabilitation, IRCCS San Raffaele Pisana, 00166 Rome, Italy
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Department of Biomolecular Science-Section of Biotechnology, University of Urbino “Carlo Bo”, 61032 Fano, Italy
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Diatheva Srl, 61030 Pesaro e Urbino, Italy
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Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, 60124 Ancona, Italy
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 2024; https://doi.org/10.3390/ijms20082024
Received: 6 March 2019 / Revised: 2 April 2019 / Accepted: 19 April 2019 / Published: 24 April 2019
(This article belongs to the Section Molecular Genetics and Genomics)
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. View Full-Text
Keywords: COPD; inhaled corticosteroid; lung function; rehabilomics; rs37972; rs471396 COPD; inhaled corticosteroid; lung function; rehabilomics; rs37972; rs471396
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Russo, P.; Tomino, C.; Santoro, A.; Prinzi, G.; Proietti, S.; Kisialiou, A.; Cardaci, V.; Fini, M.; Magnani, M.; Collacchi, F.; Provinciali, M.; Giacconi, R.; Bonassi, S.; Malavolta, M. 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. Int. J. Mol. Sci. 2019, 20, 2024.

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