Large study sheds light on the genetics behind osteoarthritis

A large study led by the University of Alabama at Birmingham has identified 10 novel regions of the genome associated with osteoarthritis and molecular targets designed to interact with them to treat osteoarthritis. A potential repurposed drug candidate has been discovered.

Osteoarthritis is a common degenerative joint disease that causes medical costs of $880 million annually in the United States alone. Nevertheless, the causative factors are still poorly understood and available treatment options are limited.

“Because no effective medical interventions are available to ameliorate the disease, osteoarthritis often progresses to the end stage, at which point the only surgical option available is usually in the form of total joint replacement. ,” writes Associate Professor Merry-Lynn McDonald. University of Alabama, and her colleagues.

“A more complete understanding of the genetic impact of osteoarthritis is essential for developing targeted and individualized therapies, ideally long before the final stages are reached.” They add in their paper. natural genetics.

The study included 484,374 participants from the Million Veteran Program (163,015 participants) and UK Biobank (321,359 participants). While the majority of participants in both studies were Caucasian (73–92%) from Europe, the Million Veterans Program also included 17.5% African American, 6.3% Hispanic, and 0.8% Asian participants. It was Similarly, the UK Biobank group contained 2.2% Africans, 0.5% East Asians and 2.2% South Asians.

The team performed a genome-wide association study (GWAS) to look for genetic associations with osteoarthritis in 140,025 cases and 344,349 controls across two cohorts. In addition to confirming several previous findings linking specific genetic variants to this condition, we also discovered 10 new regions of genomic variation associated with osteoarthritis.

For example, there was a region within chromosome 2. EFEMP1 Gene encoding fibulin-3, a protein known to contribute to the elasticity of connective tissue. Fibrin-3 levels vary among individuals with this condition and can be used as a biomarker of osteoarthritis progression.

The researchers report some indications of ancestral differences, but say studies involving larger populations of non-European ancestral populations are needed to explore this in greater depth.

The team analyzed the results to assess whether there are approved drugs that can be repurposed to treat osteoarthritis. “Our drug repurposing findings support current physician intuition regarding antiepileptic drug prescribing patterns for osteoarthritis pain,” the authors wrote. “The antiepileptic drugs gabapentin and pregabalin are prescribed for pain relief in patients with osteoarthritis despite a lack of understanding of how they work in patients with osteoarthritis. is increasing.”

The team also found expression of quantitative trait loci suggesting that some anti-cancer and anti-acne drugs may also have the potential to treat osteoarthritis.

“Many antineoplastic agents have antifibrotic properties. Synovial inflammation and fibrosis are indicative of osteoarthritis progression, and some antineoplastic agents may be beneficial in osteoarthritis.” It supports the logic that it is possible,” the researchers wrote.

“Anti-acne formulations contain azaleic acid, which was reduced in the urine of an osteoarthritis rat model. Whether urinary azaleic acid serves as a biomarker of osteoarthritis progression in humans. Additional studies are worthwhile to test.”

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