P.028 Epigenetic Interaction Between α-Adducin and Renin-Angiotensin-System Genes in Relation to the Elastic Properties of the Femoral Artery

Abstract

Background

We previously demonstrated that epigenetic interaction between the α-adducin (ADD1) Gly460Trp and the ACE I/D polymorphism modulates the properties of the femoral artery. Here, we investigated multiple-gene interactions between ADD1, ACE and other genes of the renin-angiotensin system: angiotensinogen (AGT) C-532T, G-6A, and angiotensin II receptor type 1 (AGTR1) A1166C.

Methods and results

We assessed the properties of the femoral artery with a wall-track system in a family-based random sample of 1064 subjects (participation rate 64.3%, mean age 43.6 years, 50.4% women). In population-based analyses, we computed phenotype-genotype associations, while adjusting for confounders, life style, and family clusters. In family-based analyses, we used a multivariate-adjusted quantitative transmission disequilibrium test (QTDT).

Results

In ADD1 Trp allele carriers, but not in ADD1 GlyGly homozygotes, AGTR1 AA subjects had lower femoral cross-sectional compliance (0.649 ± 0.030 vs 0.742 ± 0.029 mm²/kPa, P = 0.027) and a lower distensibil-ity coefficient (10.18 ± 0.43 vs 11.27 ± 0.41 10^-3/kPa, P = 0.067) than AGTR1 C allele carriers. QTDT confirmed these associations. The between-family component of phenotypic variability was not significant, suggesting that there was not population stratification. None of the gene-gene interactions involving AGT was statistically significant (P≥0.088).

Conclusions

The ADD1 Gly460Trp, AGTR1 A1166C and ACE I/D jointly influence the functional properties of the femoral artery.