7 potential genetic biomarkers for AS found in computer analyses

Genes may play 'important role' in immune pathways, scientists say

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Seven genes — from a pool of four dozen identified as being different in people with ankylosing spondylitis (AS) — may be potential genetic biomarkers for this rare type of arthritis, according to a new study done based on computer analyses.

The study also uncovered several molecules that may help to normalize genetic dysregulation in AS. While researchers stressed that further biological tests are needed to validate their results, they suggested that these findings could be a starting point for future investigations.

“We predicted the drugs that may have therapeutic effects on AS,” the team wrote, noting that “in recent years, there has been an increasing focus on genetic factors in AS, leading to the discovery of several drugs.”

The study, “Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis,” was published in the journal BMC Musculoskeletal Disorders.

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Potential genetic biomarkers showed good ability to ID AS

AS is characterized by inflammation in the lower joints of the spine. It’s not clear why the disease develops, though genetics are believed to play a role.

To learn more, a team of researchers in China used computer-based analyses to compare gene expression profiles among people with or without AS. Gene expression refers to the activity levels of genes — that is, the extent to which different genes are essentially turned on or off — which can strongly influence the biological activity of cells.

The analysis included gene expression data on 60 people with AS and 20 people without the disease, who served as controls; these data were collected from AS-related datasets.

In initial comparisons, the researchers identified 48 genes expressed at significantly different levels in the AS patients. Exactly half were expressed at unusually high levels, while the other 24 were expressed at low levels.

The team next conducted analyses examining the biological roles of these genes, looking at how changes in expression due to AS might influence broader cellular activity.

Many of these genes are known to be involved in regulating immune function and inflammation, which the scientists said makes sense given that AS is defined by excessive inflammation. While it’s not clear whether these genetic changes might be a cause or consequence of dysregulated inflammation in AS, the data suggest these genes could be markers of the disease.

Among all the identified genes, the researchers identified seven with central roles in the dysregulation seen in AS. These were: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP, and SORL1.

We identified seven key genes as potential markers of AS and further explored the various biological functions and pathways through which they affect AS progression, especially playing an important role in immune-related pathways.

To test whether any of them could be useful as genetic biomarkers, the team calculated a statistical measure called the area under the receiver operating characteristic curve or AUC. This statistical test measures how well a given metric — here, gene expression — can differentiate between two groups.

For this study, researchers looked at whether these potential genetic biomarkers could tell the difference between AS or not. AUC values can range from 0.5 to 1, with higher values indicating a better differentiating ability, according to the researchers.

The results showed that the AUCs for the seven genes ranged from 0.729 to 0.786 — overall suggesting a fairly good ability to tell the difference between AS and non-AS samples.

“We identified seven key genes as potential markers of AS and further explored the various biological functions and pathways through which they affect AS progression, especially playing an important role in immune-related pathways,” the researchers wrote in the study’s conclusion.

The team also conducted computer-based analyses in which they compared the genes that are dysregulated in AS, with changes in gene expression induced by various drugs. Their goal here was to identify drugs that prompted changes in the opposite direction of the changes seen in AS, such that the medications might normalize gene expression.

This analysis identified four potential therapies: over-the-counter anti-inflammatory ibuprofen, a beta-adrenergic agonist called cimaterol, the plant extract forskolin, and a bacterial toxin called bongkrek acid.

The researchers stressed that these results are based only on computer analyses, so further tests will be needed to verify whether these drugs actually have an effect on gene dysregulation or disease activity in AS. Still, they said these data may lay the groundwork for future investigations, noting that the information they uncovered “provides a new direction for further exploring the pathogenesis [disease development] of AS and improving the diagnosis and management of AS cases.”