AHSGfetuinA

AHSG, also known as alpha-2-HS-glycoprotein or fetuin-A, is a secreted plasma glycoprotein encoded by the AHSG gene in humans. The protein is produced predominantly by liver hepatocytes and released into the circulation, where it circulates at relatively high levels. Fetuin-A is heavily glycosylated and phosphorylated in its mature form.

Fetuin-A functions as a systemic inhibitor of ectopic calcification by binding calcium and phosphate and stabilizing calciprotein particles, which helps prevent mineral precipitation in soft tissues. It also participates in processes related to bone mineralization and can influence inflammatory signaling and innate immune responses.

In metabolism and inflammation, fetuin-A modulates insulin signaling. Experimental studies show that higher levels can impair insulin receptor signaling and contribute to insulin resistance in rodents, while human observational data link elevated fetuin-A with metabolic syndrome and an increased risk of type 2 diabetes. The protein is thought to act as a hepatokine with diverse metabolic effects, though its roles can be context-dependent.

Clinical relevance and genetics: Altered fetuin-A levels have been associated with metabolic and inflammatory conditions. In chronic kidney disease, reduced fetuin-A is linked to increased vascular calcification, whereas higher circulating levels correlate with insulin resistance in some populations. Genetic variants in the AHSG gene influence circulating fetuin-A concentrations and relate to variation in metabolic traits among individuals.

Overall, fetuin-A is a conserved, liver-derived protein with a dual role in mineral metabolism and metabolic regulation, making it a focus of research as a potential biomarker and therapeutic target in disorders of calcification and metabolic disease.