Ontology highlight
ABSTRACT: Introduction
Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. Aim: To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C TNF-α polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis.Material and methods
Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for TNF-α polymorphisms: -1031 T/C, -857C/T, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal.Results
No correlation between the initial clinical presentation of sarcoidosis and TNF α polymorphisms was found, neither for every allele nor for combined genotypes distribution. According to PFT evaluation we have discovered 3 types of response to MTX: early (ER), late (LR) and No-response (NR). TNF-α-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. TNF-α-308 GG genotype transferred the 3-fold higher probability of early vs late response to MTX, p=0.02. Combined genotyping allowed to distinguish LR from ER and NR groups. ER and NR patients are genetically similar (-857CC-308GG). LR are "genetically" different group of patients (-857C/T-308GG or -857CC-308A/G) with 5-fold greater probability to be LR than TNF-α-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. TNF-α-308GG-857CC patients have significantly lower chance to be LR comparing to other response type p=0.03 OR=0,075 95% CI=0.07-0.08.Conclusion
Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene.
SUBMITTER: Goljan Geremek A
PROVIDER: S-EPMC7247097 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Goljan Geremek Anna A Puscinska Elzbieta E Czystowska Monika M Skoczylas Agnieszka A Bednarek Michal M Nowinski Adam A Gorecka Dorota D Demkow Urszula U Sliwinski Pawel P
Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG 20190501 4
<h4>Introduction</h4>Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. <i>Aim:</i> To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C <i>TNF-</i>α polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis.<h4>Material and methods</h4>Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for <i>TNF-</i>α polymorphisms: -1031 T/C, -857C/T, ...[more]