rs4963

This study demonstrates that α- and β-adducin polymorphisms affect podocyte protein expression and proteinuria in rodent models and are associated with the rate of renal function decline in human IgA nephropathy patients. The ADD2 1797T variant (rs4984) showed significant association with GFR decline (β=-4.66, p=0.0043), with significant interaction with ADD1 460Trp (rs4961, p=0.0174). Targeted deletion of β-adducin in mice reduced proteinuria and increased podocyte protein expression, while introduction of the polymorphic MHS β-adducin locus in normotensive rats caused early reduction in podocyte proteins, glomerular lesions, and proteinuria.

A study of 2,746 Han Chinese participants from 636 families examined associations between 12 SNPs in GNB3 and ADD1 genes and blood pressure (SBP, DBP, MAP). The GNB3 SNP rs4963516 showed significant association with diastolic blood pressure and mean arterial pressure, with CC homozygotes having 2.35 mmHg higher DBP (P=0.0002) and 2.45 mmHg higher MAP (P=0.0004) compared to A allele carriers, suggesting a role for GNB3 in blood pressure regulation in Chinese populations.