Pam Harrison

June 23, 2015

ROME — In patients with ankylosing spondylitis, smoking might interact with epigenetic factors and promote radiographic progression, according to the first study of its kind.

In an investigation of the link between spondylitis and epigenetic variants, the researchers "uncovered a significant association between smoking, methylation status, and radiographic progression," Proton Rahman, MD, from Memorial University in St. John's, Newfoundland, told reporters.

The team hypothesized that "environmental triggers such as smoking could lead to epigenetic changes that accelerate the damage caused by the disease and that investigating the mechanisms that control these changes could lead to novel therapeutic targets for ankylosing spondylitis," he explained here at the European League Against Rheumatism Congress 2015.

The researchers evaluated clinical, radiographic, and DNA information for 76 patients from the University of Toronto.

All patients had undergone serial radiographic imaging on average every 3 years, and 35 had evidence of radiographic progression, defined as any change in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).

For the entire cohort, the mean radiographic progression score was approximately 1 mSASSS unit per year.

Of the 20 previously identified epigenetic variants that potentially affect ankylosing spondylitis, seven were found to be particularly relevant.

On multiple linear regression with these seven variants, the researchers identified an association between smoking and the risk for radiographic progression.

In fact, progression was 0.13 units higher in smokers than in nonsmokers, "although the effect of smoking itself on radiographic progression was not statistically significant," Dr Rahman reported.

The team also found that a change of 1% in methylation status meant an increase of 1 mSASSS unit per year of radiographic progression.

And "when patients smoked, that rate went up; a 1% change in methylation status caused a 2 unit increase in mSASSS per year," Dr Rahman added.

Although a 2 unit increase in mSASSS per year might not sound like much, "if you think of it as a 5% change, that means there will be a progression of 10 units per year, which is quite significant," he explained.

In contrast, for patients who did not smoke but who had evidence of hypermethylation, there was no radiographic progression.

"Some patients can have ankylosing spondylitis for a long time and not progress radiographically, so there is no disabling disability. Others, however, progress really quickly," Dr Rahman said.

Epigenetic Changes

"We think it's the interaction between smoking and epigenetics that is leading to radiographic progression. This means that from a practical perspective, ankylosing spondylitis patients should be discouraged from smoking," he concluded.

These data on smoking and the clinical progression of ankylosing spondylitis are of the utmost importance because they can help clinicians better understand the pathogenesis of the disease, said session cochair Marina Frleta, MD, from the University of Glasgow in the United Kingdom.

"However, tackling this topic is not without its difficulties. There are many confounding factors that add to the complexity of the interpretation of the data," Dr Frleta told Medscape Medical News.

For example, it would have been very informative to have information on how long and how much the patients in this study smoked.

Dr Frleta suggested that because ankylosing spondylitis doesn't always have steady radiographic progression, "a longer follow-up is necessary to distinguish between the natural course of the disease, the effect of medications, and the epigenetic status" of patients, particularly those who smoke.

Because it is difficult to exclude epigenetic patterns related to ankylosing spondylitis that might have been present before the methylation status of the patients was ascertained, "I look forward to the future development of these data," she said. In addition, "a larger, well-characterized cohort would be very informative."

Dr Rahman and Dr Frleta have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2015: Abstract OP0206. Presented June 12, 2015.

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