Gene-Environment Interplay in Hyperinsulinemia and Serum Urate Regulation via SLC22A12: Implications for Personalized Hyperuricemia Management

Highlight

• Hyperinsulinemia inversely correlates with fractional excretion of urate (FEUA), implicating URAT1-mediated urate reabsorption in hyperuricemia.
• Phosphorylation of URAT1 at Thr408 by AKT and SGK1 kinases, induced by hyperinsulinemia and high salt intake, respectively, increases URAT1 activity and serum urate levels.
• Genetic variants of SLC22A12 (notably rs147647315 and rs475688) modulate the impact of hyperinsulinemia on serum urate, highlighting gene-environment interactions.
• These findings support personalized approaches to hyperuricemia treatment considering metabolic status and genetic background.

Study Background and Disease Burden