IS THERE A GENETIC PREDISPOSITION TO FROZEN SHOULDER? A Systematic Review and Meta-Analysis

Background: Frozen shoulder is a common disorder that leads to substantial functional loss for patients by impairing activities of daily living. It also adversely affects patients and society by impairing the ability to work. Its pathogenesis is not fully understood. The aim of the present study was to perform a systematic review and meta-analysis to assess the evidence suggesting a genetic link to frozen shoulder. Methods: A literature search of MEDLINE, EMBASE, and CINAHL databases using relevant keywords revealed 5506 studies. After appropriate screening of titles, abstracts, and full studies, seven studies were analyzed. Results: Three studies investigated rates of frozen shoulder among relatives. One study (n = 1828 twin pairs) showed an 11.6% prevalence in twin pairs and demonstrated a heritability of 42% for frozen shoulder after adjusting for age. A second study (n = 273) showed that 20% of patients with frozen shoulder had a positive family history involving a first-degree relative. The relative risk of frozen shoulder was 4: 1 when all patients with frozen shoulder were compared with a control population. A third study (n = 87) showed that 29% of patients with frozen shoulder had a first-degree relative with frozen shoulder. Two studies evaluated racial predilection for frozen shoulder. One study (n = 50) reported a substantially higher number of white patients (76%) with frozen shoulder than black patients (24%). A second study (n=87) showed that being born or having parents or grandparents born in the British Isles were risk factors for frozen shoulder. Four immunological studies investigated human leukocyte antigen (HLA)-B27 as a risk factor for frozen shoulder. Meta-analysis of two of these studies with clearly defined controls showed significantly higher rates of HLA-B27 positivity in patients with frozen shoulder as compared with controls (p < 0.001). Conclusion: The limited evidence points toward a genetic link to frozen shoulder. We used family history and racial predilection as markers for genetic association, both of which indicated the presence of a genetic predisposition to frozen shoulder. However, as there is a lack of unbiased genetic approaches, there is an opportunity for genome-wide association studies to address definitively the molecular genetics of frozen shoulder. Such studies may eventually lead to a better understanding of the pathogenesis of frozen shoulder and the development of novel therapeutic interventions.