biostudies-literatureUnknown36(4)Goljan Geremek A<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, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal.<h4>Results</h4>No correlation between the initial clinical presentation of sarcoidosis and <i>TNF</i> 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). <i>TNF-</i>α-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. <i>TNF-</i>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 <i>TNF-</i>α-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. <i>TNF-</i>α<i>-</i>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.<h4>Conclusion</h4>Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG261-273https://www.ebi.ac.uk/biostudies/studies/S-EPMC7247097biostudies-literatureMethotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.PMC7247097Puscinska EGorecka DDemkow UNowinski ACzystowska MGoljan Geremek ABednarek MSliwinski PSkoczylas AfalseMethotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.<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, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal.<h4>Results</h4>No correlation between the initial clinical presentation of sarcoidosis and <i>TNF</i> 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). <i>TNF-</i>α-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. <i>TNF-</i>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 <i>TNF-</i>α-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. <i>TNF-</i>α<i>-</i>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.<h4>Conclusion</h4>Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene.2019-01-01T00:00:00Z20192024-11-13T11:56:48.852Z2020-06-03T07:04:10ZS-EPMC72470973247696210.36141/svdld.v36i4.7708