OSM and Cardiovascular Disorder

This summary evaluates the association between Oncostatin M (OSM) (HGNC:8506) and cardiovascular disorder (MONDO_0004995). Several multi‑patient studies have interrogated common genetic variants and inflammatory signatures to explore the role of the OSM signaling pathway in cardiovascular phenotypes. In one study investigating carotid plaque vulnerability, variants in the OSM receptor locus provided modest associations with plaque composition but were not significantly linked to overall cardiovascular disease risk (PMID:33959646).

A separate transcriptomic investigation in psoriasis identified an inflammatory signature that included OSM among several cytokine regulators, with this signature associating with both prevalent myocardial infarction and future cardiovascular events (PMID:36924033). However, these associations arise from expression profiling rather than direct variant‑driven genetic evidence.

Genetic evidence for OSM is thus limited. No definitive pathogenic coding changes or familial segregation patterns have been reported for OSM in the context of cardiovascular disorders. The studies rely on common variant associations and transcriptomic data rather than the demonstration of deleterious variants in OSM itself. This has resulted in a ClinGen tier of Limited evidence for genetic causality in this setting.

Experimental assessment of OSM function, however, is supported by robust functional studies establishing its role as a cytokine with a well‑defined receptor binding mechanism and downstream signaling activity (PMID:2026606). While these functional assays confirm the biological activity of OSM, they have not directly corroborated its pathogenicity in cardiovascular disease. Hence, the functional evidence, though supportive of the protein’s activity, remains only moderately convincing in linking OSM perturbation to cardiovascular phenotypes.

Integrating the genetic and experimental data, the overall association between OSM and cardiovascular disorder is best categorized as Limited. The available studies reveal a possible contribution of the OSM pathway to intermediate cardiovascular traits such as plaque vulnerability and inflammatory profiles, yet fall short of establishing a direct causative connection that would support clinical diagnostic application. Further investigation is needed to clarify the potential impact of OSM dysregulation within the multifactorial context of cardiovascular disease.

Key take‑home: Although OSM plays a critical role in cytokine signaling, current evidence does not substantiate a strong direct causal link between OSM variants and cardiovascular disorder, underlining the need for more targeted genetic studies.

References

• Frontiers in cardiovascular medicine • 2021 • Common Variants Associated With OSMR Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans PMID:33959646
• Journal of the European Academy of Dermatology and Venereology: JEADV • 2023 • An inflammatory transcriptomic signature in psoriasis associates with future cardiovascular events PMID:36924033
• The Journal of biological chemistry • 1991 • Disulfide bond assignment and identification of regions required for functional activity of oncostatin M PMID:2026606

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