P-284: Combined effects on vascular wall characteristics of the ACE I/D polymorphism and mutations of the A-B-Γ adducin genes
We recently found that the intima-media thickness (IMT) of the muscular femoral artery but not the elastic carotid artery, increased with the number of D alleles of the angiotensin-converting enzyme gene (ACE/D). This increase was restricted to carriers of the D allele also having the α-adducin Trp...
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Published in | American journal of hypertension Vol. 14; no. S1; pp. 123A - 124A |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford University Press
01.04.2001
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Subjects | |
Online Access | Get full text |
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Summary: | We recently found that the intima-media thickness (IMT) of the muscular femoral artery but not the elastic carotid artery, increased with the number of D alleles of the angiotensin-converting enzyme gene (ACE/D). This increase was restricted to carriers of the D allele also having the α-adducin Trp allele (α-ADD/Trp). Recently, mutations of the β- and γ-unit of the adducin dimeric molecule (α/β or α/γ) have been described, but have not yet been studied in relation to vascular wall characteristics. We therefore investigated whether mutations in β- and γ-adducin (β-ADD/Val, γ-ADD/G) modulate the combined effects of the ACE and α-adducin genes on femoral IMT. We also investigated the associations between these genes and carotid IMT and aortic pulse wave velocity (PWV). We used an ultrasound-based wall tracking system to measure carotid and femoral IMT and PWV in 380 subjects enrolled in a population study. Subjects were genotyped for the presence of ACE/D, α-ADD/Trp, β-ADD/Val, and γ-ADD/G. Statistical analysis allowed for confounders. The sample included 192 women (50.5%) and 188 men (49.5%). Age ranged from 12 to 76 years (mean 39.8). Carotid and femoral IMT averaged 575 μm and 719 μm, respectively. Mean PWV was 6.04 m/s. In single gene analyses, none of the adducin polymorphism had an effect. Combinations of the α/β and the α/γ mutations had no effect with the exception of the α/β variation in relation to femoral IMT. The ACE/D allele was associated with increased femoral IMT (+73 μm). The effect of the ACE/D allele on femoral IMT did not change significantly in the presence of the α-adducin mutation when the β-mutation was absent. In the presence of both the α- and β- adducin mutation the increase of femoral IMT with the ACE/D allele rose to 147 μm. In conclusion, this study expands our earlier finding of an increased IMT of the femoral artery in the presence of both the ACE/D allele and the α-ADD/Trp allele. However, mutation of the β-adducin also seems to be a necessary modulator to express the additive effects of the ACE/D and α-adducin Trp alleles on femoral IMT. |
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Bibliography: | href:14_S1_123Ab.pdf ark:/67375/HXZ-ZTZ1C8XP-R istex:15B9D2F901797F20F2328E82F9A801CA4519F662 |
ISSN: | 0895-7061 1879-1905 |
DOI: | 10.1016/S0895-7061(01)01455-8 |