New findings point to specific genes that are linked to an increased risk of frozen shoulder

New findings point to specific genes that are linked to an increased risk of frozen shoulder

Frozen shoulder or adhesive capsulitis is a common cause of shoulder pain and immobility. New evidence points to specific genes associated with an increased risk of this condition, reports The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in collaboration with Wolters Kluwer.

The risk genes are associated with a nearly sixfold increase in the likelihood of developing frozen shoulder—a stronger association for most known clinical risk factors, according to new research by Mark T. Langhans, MD, PhD, of the Hospital for Specialty Surgery, New York. The authors believe their findings may provide new insights into the causes, prevention and treatment of adhesive capsulitis.

Genome-wide association study finds “significant loci” that influence the risk of frozen shoulder

Patients with adhesive capsulitis develop a painful and progressive loss of shoulder motion with associated pain. Frozen shoulder is one of the most common shoulder disorders, affecting up to 10% of people at some point in their lives. Although the exact cause is unclear, frozen shoulder sometimes occurs after an injury, surgery, or other condition that limits shoulder mobility. The loss of motion results from fibrosis (scarring or thickening) of the capsule around the shoulder joint.

Certain clinical factors are associated with an increased risk of frozen shoulder, including diabetes, thyroid disease and smoking. Recent studies suggest the risk is also higher in people with affected relatives - suggesting a possible genetic predisposition. Dr. Langhans and colleagues conducted a genome-wide association study to identify specific genes that may be associated with the risk of frozen shoulder.

Data from large British database examined

The study used data from a large British database, the UK Biobank, which contains genetic and health data from approximately 500,000 patients. The analysis focused on 2,142 patients with adhesive capsulitis compared to patients without this diagnosis. Potential genetic associations were adjusted for other factors, including gender, diabetes, thyroid disease, history of shoulder dislocation, and smoking.

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The study identified three significant loci for frozen shoulder. The strongest association was found for gene variants located at a site called WNT7B. This result was consistent with previous studies that reported a possible association between WNT7B and frozen shoulder along with several other orthopedic diseases. Weaker associations were also found for two previously unreported genetic loci located near genes for POU1F1 and MAU2.

All three associations remained significant after adjusting for other factors. Together, the three variants resulted in an almost sixfold increase in the likelihood of developing frozen shoulder. That was greater than the risk associated with diabetes (about four times) or thyroid disease (less than two times), and was exceeded only by smoking (about 11 times).

New insights could lead to new developments

The results may provide new insights into the development of adhesive capsulitis. In particular, genes located at WNT7B have been shown to be expressed in bone-forming cells (osteoblasts) and are involved in the regulation of fibrosis, among a variety of other functions. The two newly reported loci, POU1F1 and MAU2, are involved in cell division, which may provide clues to the cellular mechanism by which frozen shoulder develops.

The researchers note some key limitations to their analysis, including the need for further studies of genetic associations in groups other than the white, British population that predominates in the UK Biobank.

Meanwhile, the new study identifies multiple genetic loci with the ability to predict clinically relevant risk of frozen shoulder. Dr. Langhans and colleagues conclude: "Refining the genetic risk metric and incorporating it into a larger clinical model could allow for the identification of patients at risk for future adhesive capsulitis, leading to prevention efforts, early detection, and ultimately improved outcomes."

Source:

Wolters Klüwer

Reference:

Kulm, S., et al. (2022) Genome-wide association study of adhesive capsulitis suggests significant genetic risk factors. Journal of Bone and Joint Surgery. doi.org/10.2106/JBJS.21.01407.

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