Ankylosing spondylitis genes, potential treatments ID’d: Study
A bioinformatics analysis was used to find changed activity in genes
Genes involved in ankylosing spondylitis (AS) as well as potential new therapies have been identified through a computer-based analysis, according to a study.
The findings “contribute to our understanding of the molecular mechanisms underlying the onset and progression of AS. They also provide candidate targets for the diagnosis and treatment of AS,” the researchers wrote in “Screening and identification of key chromatin regulator biomarkers for ankylosing spondylitis and drug prediction: evidence from bioinformatics analysis,” which was published in BMC Musculoskeletal Disorders.
AS is a type of arthritis marked by inflammation in the sacroiliac joint, where the base of the spine meets the pelvis. Although the exact mechanisms of its development aren’t fully understood, genetic and environmental factors are believed to play a role.
Variants in the human leukocyte antigen B27 (HLA-B27) gene are an established risk factor. HLA genes carry instructions for proteins that regulate immune responses.
Researchers in China used a type of computer analysis called bioinformatics to identify genes with changed expression (activity), either higher or lower, in AS compared to healthy people to assess other genes in the disease.
New genes, possible treatments in AS
The researchers used the dataset GSE25101 from the Gene Expression Omnibus public repository that includes genetic data from tissue samples of people with AS and healthy people.
They identified chromatin regulator genes that were differentially expressed — 24 were less active, four were more active — with AS. Chromatin regulators control if genes are “on” or “off” through the effects on histones and chromatin. Histones are proteins that form a complex called chromatin with DNA.
The top 10 hub genes were EP300, DNMT1, TRIM28, SETD1A, DDB1, MTA2, EP400, PARP1, BAZ1B, and CBX1. Hub genes have interactions with other genes and play key roles in biological processes.
Given the link between AS and the immune system, the investigators then matched and scored the AS dataset with immune-related genes. Comparing patients and health people revealed significant activity differences in genes related to inflammation, T-helper cells, and tumor-infiltrating lymphocytes. T-helper cells are a key part of adaptive immunity by detecting infections and activating other immune cells to fight them. Tumor-infiltrating lymphocytes are lymphocytic cell populations that have invaded a tumor.
Taking into account the hub genes identified, the scientists conducted a drug prediction analysis. The compounds that may have a therapeutic effect included BAY 11–7082 and myricetin. Both have anti-inflammatory properties that inhibit the signaling mediated by tumor necrosis factor (TNF)-alpha, a major pro-inflammatory molecule thought to be important in autoimmune diseases, such as AS. Myricetin is a natural component found in herbs, berries, and tea leaves.
“The use of BAY 11–7082 and myricetin to reduce the expression of TNF-α and thus alleviate the symptoms of AS is a novel therapeutic idea,” the researchers wrote, noting the study’s results both confirm previous findings and provide new directions for diagnosing and treating AS. “Validation through cell and animal experiments will be conducted in later stages,” they said.