Sev eral of these proteins were likewise identified in our uni variate selleck compound analyses. The STX17 marker was one of three proteins whose altered plasma levels was unique to the comparison of discor dant MZ twins, while PON1 was the only marker identi fied with statistically different levels in each of the three two group comparisons. The PON1 gene product, paraoxonase 1, is an aryles terase that serves an important role in several physiolo gical pathways including the detoxification of xenobiotics most notably organophosphorus metabo lites associated with pesticide exposures as well as reducing oxidative damage when associated with circu lating high and low density lipoproteins.

Inter estingly, functional polymorphisms in the PON1 gene influence expression Inhibitors,Modulators,Libraries levels and activity of the enzyme and have been associated with several immune mediated conditions, atherosclerotic risk, and possibly influence responses to anti TNF a therapy in RA. Several independent lines of evidence implicate reduced plasma PON1 levels as a potential biomarker for a subset of SAID. In our present study, we observed an apparent gradient of decreasing PON1 levels among our three study groups in univariate analyses whereby PON1 levels were lowest in SAID affected Inhibitors,Modulators,Libraries twins and highest in unrelated controls. Also, PON1 was Inhibitors,Modulators,Libraries identified as an informative marker in a mul tivariate RF model, which effectively segregated SAID affected vs. unaffected twins. In molecular pathway modeling, PON1 mapped as a central node in interac tions predicted among all the relevant factors in the RF analysis.

More recently, Inhibitors,Modulators,Libraries certain PON1 polymorphic var iants were implicated as risk factors for other chronic inflammatory diseases, including RA and types 1 and 2 diabetes. Plasma protein blot analysis of our twin pairs and matched, unrelated controls demon strated reduced plasma PON1 levels in 50% of the twin cases independent of disease phenotype. We speculate that shared or similar environmental factors, such as pesticide exposures, might influence the development of different SAID by a common mechanism. There are several limitations to our plasma proteomics study design. Most importantly, small sample sizes and the resulting decrease in statistical power owing to the difficulties associated with the identification and recruit ment of SAID discordant MZ twins with recent disease onset.

Also, the heterogeneity of human study subjects, including variations in environmental exposures, clinical phenotypes, disease activity and duration and immuno suppressive therapies may influence plasma protein composition and present potential confounders. Addi tionally, given the capacity of mass spectrometric Inhibitors,Modulators,Libraries techni ques to detect several thousand component peaks from individual plasma samples, www.selleckchem.com/products/Trichostatin-A.html higher false discovery rates are anticipated in the absence of corrections for multiple statistical comparisons.