alexa T-889C IL-1alpha promoter polymorphism influences the response to oral cyclophosphamide in scleroderma patients with alveolitis.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Computer Science & Systems Biology

Author(s): Beretta L, Cappiello F, Barili M, Bertolotti F, Scorza R

Abstract Share this page

Abstract Cyclophosphamide (CYC) is the cornerstone of the treatment of systemic sclerosis (SSc)-associated fibrosing alveolitis (FAS). Despite treatment with CYC, in a not negligible proportion of SSc-FAS patients, deterioration in lung function can be observed. Interleukin-1 (IL-1) cluster gene single nucleotide polymorphisms (SNPs) were implicated in the pathogenesis of some interstitial lung diseases and may favor the progression of restrictive lung disease in SSc. The present retrospective case-control study was conducted on 18 SSc patients previously treated with oral CYC (2 mg/kg) and medium-dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day) for the presence of FAS-defined as the presence of areas of ground-glass attenuation on high-resolution computed tomography (HRCT) and a recent deterioration in lung function. The T/C substitution at position -889 of the IL-1alpha promoter gene (T-889C) was determined by polymerase chain reaction and restriction length fragment analysis. Patients carrying the T allele showed a significant decrease in forced vital capacity (FVC) values after 12 months of therapy (2.46+/-1.09 vs 2.59+/-1.17 l), while wild-type patients showed an increase in FVC values (2.73+/-0.54 vs 2.54+/-0.5 l) (p=0.005 between the two groups, analysis of variance for repeated measures). Patients with the T-889C polymorphism presented higher baseline erythrocyte sedimentation rates (ESR) compared to wild-type patients (50.3+/-25.4 vs 23.3+/-17.7 mm/h). Baseline ESR inversely correlated with the variation of FVC (DeltaFVC) after 12 months of therapy (r=-0.50 and p<0.05). The two groups were otherwise similar with respect to autoantibodies, age, disease duration, disease subset, radiological HRCT grade, and baseline lung physiology. The T-889C polymorphism represents a marker for worse functional responses to CYC in SSc-FAS. The mechanisms by which this SNP may negatively influence the response to CYC therapy are unknown, but might be linked to increased inflammatory responses in the lungs. This article was published in Clin Rheumatol and referenced in Journal of Computer Science & Systems Biology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version