Potential AS genetic biomarkers identified in study

The PPARG and MDM2 genes hold the most promise, researchers say

Lindsey Shapiro avatar

by Lindsey Shapiro |

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Genetic analyses revealed a number of genes with altered activity in ankylosing spondylitis (AS) patients compared with healthy people, which researchers believe could serve as novel disease biomarkers.

Among them, the PPARG and MDM2 genes — both of which are involved in inflammation — were found to hold the most promise.

Researchers also identified pathways involved in stress of the endoplasmic reticulum (ER) — a cellular compartment involved in protein synthesis, folding, and transport — were altered in AS, possibly indicating that changes in the ER help to drive AS development.

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Potential blood biomarkers for AS identified in study

The study, “RNA sequencing and bioinformatics analysis of differentially expressed genes in the peripheral serum of ankylosing spondylitis patients,” was published in the Journal of Orthopaedic Surgery and Research.

A chronic inflammatory disease, AS is thought to arise from a combination of environmental and genetic factors, but not many genes have been associated definitively with AS. The discernment of such genes could help scientists to develop AS biomarkers and better understand disease mechanisms.

“There is an urgent need to identify new biomarkers that can act as reliable diagnostic or prognostic indicators of AS,” the researchers wrote. “Such biomarkers will be invaluable in the prevention, treatment, and control of this disease.”

To learn more, researchers at the the Affiliated Hospital of Qingdao University, in China, conducted a genetic analysis of blood samples from three AS patients and three healthy people seen at their hospital.

There, they identified 100 genes that had significantly different expression, or activity, in AS patients relative to healthy people. Of these so-called differentially expressed genes (DEGs), 49 had higher activity in AS and 51 had lower activity.

A closer look revealed that many of these DEGs were involved in signaling pathways associated with the ER. The most significantly affected pathway was protein processing in the ER. Other affected processes included response to ER stress — which happens when the capacity for the ER to fold proteins becomes saturated — as well as the unfolded protein response, which serves as a buffer to prevent ER stress.

Activation of neutrophils, a type of immune cell, and apoptosis, or programmed cell death, also were among the altered pathways.

Reinforcing previous research

These findings are in agreement with previous studies that have suggested ER stress and associated pathways might play a critical role in AS onset and progression, according to the team.

A group of the top 10 genes that differentiated AS were identified, the most significant of which were PPARG and MDM2. Ultimately, the researchers determined these two genes were the most useful for distinguishing AS, and thus may be good disease biomarkers.

PPARG is a gene involved in regulating inflammation and has been previously linked to AS and other autoimmune diseases. MDM2 provides instructions to produce a multifunctional protein involved in certain inflammatory signaling pathways, and also has been associated with autoimmune diseases.

“These hub genes thus regulate immune-related diseases and have the potential to serve as diagnostic and therapeutic targets in these diseases,” the researchers wrote.

Overall, “our results may provide a theoretical basis for further studies to elucidate the molecular mechanism of AS and provide more therapeutic targets for future clinical interventions,” the team concluded.