Relationship Between Insulin-Like Growth Factor 2 Receptor and Coronary Artery Disease.

OBJECTIVE

Relationship between insulin-like growth factor 2 receptor (IGF2R) and coronary artery disease (CAD) remains unclear. We aimed to explore associations of IGF2R with CAD incident and death from CAD.

METHODS

The prospective analysis was conducted based on the cohort of UK Biobank, which included 51 581 participants with plasma IGF2R concentration and 487 034 participants with genetic data. We derived a polygenic risk score for IGF2R expression based on a Bayesian regression framework that incorporates genome-wide association study summary statistics. Main outcomes included CAD incident and CAD mortality. We conducted another analysis based on donors of human liver specimens. The hepatic level of IGF2R was compared between 10 donors with CAD and 11 without CAD, which was detected by immunohistochemistry.

RESULTS

After adjusting potential confounders, one-unit increment of plasma IGF2R was associated with a 39% higher risk of CAD incident and a 60% higher risk of CAD mortality. Comparing to low tertile of plasma IGF2R normalized protein expression, participants with high tertile of IGF2R showed higher risk of CAD incident (hazard ratio: 1.23, 95% CI 1.13-1.33) and CAD mortality (hazard ratio: 1.30, 95% CI 1.01-1.68). One-unit increment in IGF2R polygenic risk score was associated with a 4% higher risk of CAD incident and 5% higher risk of CAD mortality. CAD cadaveric donors showed 120% higher hepatic IGF2R level than free of CAD cadaveric donors (2.20 ± 1.53 vs 1.00 ± 0.96, P < .01).

CONCLUSION

Higher levels of IGF2R are associated with an increased risk of incident CAD and CAD-related mortality.