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Epigenetics May Alter Disease Progression and Biologic Response in SpA

June 12 2015 2:58 PM ET via RheumReports RheumReports

Epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence. In other words, there is a change in the phenotype without a change in the genotype. This is usually due to environmental factors. Smoking is a well-recognized risk factor for epigenetic modifications.

O’Rielly et al studied whether there is an interaction between smoking and epigenetics that leads to increased radiographic progression in AS. This question was proposed since clinical studies have shown that smokers are more likely to exhibit radiographic progression.

They examined the methylation pattern of 20 pre-selected genes in 75 AS patients who had serial radiographs approximately 3 years apart. Smokers with low methylation scores had a significantly higher rate of radiographic progression. Every 1% difference in methylation score translated to an increase of 2 mSASSS units/yr of radiographic progression.

This is the first study to demonstrate how an interaction between smoking and epigenetic factors can influence radiographic progression in AS and adds further ammunition to why AS patients should be discouraged from smoking.

In a second study by the same group, epigenetics was examined as a proposed mechanism for secondary failure to TNF inhibitors. Genome-wide epigenetic changes among TNFi responders and TNFi secondary failures in PsA patients were studied.

Twenty patients with secondary TNFi failure were evaluated (of which 15 were treated with etanercept and 5 with adalumimab) after a mean treatment duration of 18 months prior to secondary failure. Twenty-one PsA patients were classified as TNFi responders as they were responding after a mean duration of 36 months (13 were treated with etanercept and 8 with adalumimab).

Genome-wide DNA methylation profiling with ~480,000 different CpG sites per sample were performed. Multiple candidates were identified for TNFi failure and response, after adjustment for multiple testing.

TNFi secondary failure genes included CD70 (encoded protein is a ligand for TNFRSF27/CD27), and TNFRSF1B (a member of the TNF receptor superfamily that mediates most of the metabolic effects of TNFα). TNFi responders included TRAPPC9 (functions as an activator of NFkB) and PSORSC13.

These preliminary results demonstrate that the global DNA methylation pattern differs between TNFi responders and secondary failures. It also raises an intriguing possibility of epigenetics as a potential mechanism of secondary failure to TNFi.

References:

INTERACTIONS BETWEEN SMOKING AND METHYLATION STATUS IS HIGHLY PREDICTIVE OF RADIOGRAPHIC PROGRESSION IN ANKYLOSING SPONDYLITIS [OP0206]

D. D. O'Rielly 1, N. Haroon2, Z. Gao1, Y. Zhang1, D. Codner1, G. Zhai1, A. Dohey1, A. Zhou1, N. Al Ghanim1, S. Hamilton1, R. D. Inman2, P. Rahman1

1Faculty of Medicine, Memorial University of Newfoundland, St. John's, 2Faculty of Medicine, University of Toronto, Toronto, Canada

GLOBAL DNA METHYLATION PATTERNS DIFFER BETWEEN RESPONDERS AND NON-RESPONDERS IN PSORIATIC ARTHRITIS PATIENTS TREATED WITH TUMOR NECROSIS FACTOR-Α INHIBITORS [OP0200]

D. D. O'Rielly 1, Y. Zhang1, D. Codner1, A. Dohey1, A. Zhou1, N. Al Ghanim1, S. Hamilton1, G. Zhai1, P. Rahman1,1,1

1Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada


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About the Author

Dr. Proton Rahman
Dr. Proton Rahman

Proton Rahman, MD is a Clinician Scientist at Memorial University of Newfoundland, where he is also Associate Dean of Clinical Research and a University Research Professor. He practices rheumatology at Eastern Health in St. John’s, Newfoundland.

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