Background: Adducin is a membrane skeleton protein, which consists either of α- and ß- or α- and γ-subunits. We investigated whether arterial characteristics might be related to the genes encoding ADD1 (Gly460Trp), ADD2 (C1797T) and ADD3 (A386G).

Methods: We randomly recruited 1126 Flemish subjects (mean age, 43.8 years; 50.3% women). Using a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries. We studied multivariate-adjusted phenotype-genotype associations, using a population- and family-based approach.

Results: In single-gene analyses, brachial diameter was 0.15 mm (P=0.0022) larger, and brachial distensibility and cross-sectional compliance were 1.55 10⁻³/kPa (P=0.013) and 0.017 mm²/kPa (P=0.0029) lower in ADD3 GG than ADD3 AA homozygotes with an additive effect of the G allele. In multiple-gene analyses, the association of brachial diameter and distensibility with the ADD3 G allele only occurred in ADD1 GlyGly homozygotes. Otherwise, the associations between the arterial phenotypes in the 3 vascular beds and the ADD1 or ADD2 polymorphisms were not significant. In family-based analyses, the multivariate-adjusted heritability was 0.52, 0.38 and 0.30 for brachial diameter, distensibility, and cross-sectional compliance, respectively (P<0.001). There was no evidence for population stratification (0.07≤P≤0.96). Transmission of the mutated ADD3 G allele was associated with smaller brachial diameter in 342 informative offspring (−0.12±0.04 mm; P=0.0085) and in 209 offspring, who were ADD1 GlyGly homozygotes (−0.14±0.06 mm; P=0.018).

Conclusions: In ADD1 GlyGly homozygotes, the properties of the brachial artery are related to the ADD3 (A386G) polymorphism, but the underlying mechanism needs further clarification.