Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.
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.
['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|']
D000328:Adult D005260:Female D006579:Heterozygote D006720:Homozygote D006801:Humans D007166:Immunosuppressive Agents D008168:Lung D008297:Male D008727:Methotrexate D008875:Middle Aged D000071184:Pharmacogenomic Variants D011110:Polymorphism, Genetic D020127:Recovery of Function D017565:Sarcoidosis, Pulmonary D013997:Time Factors D016896:Treatment Outcome D014409:Tumor Necrosis Factor-alpha
treatment sarcoidosis TNF-α polymorphism MTX