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Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2000 Jun; Vol. 20 (6), pp. 1600-5. - Publication Year :
- 2000
-
Abstract
- A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.
- Subjects :
- Adult
Alleles
Arteriosclerosis genetics
Blood Flow Velocity
Blood Glucose analysis
Blood Pressure
Hemorheology
Heterozygote
Homozygote
Humans
Lipids blood
Male
Matrix Metalloproteinase 3 blood
Middle Aged
Polymorphism, Genetic
Risk Factors
Ultrasonography
Carotid Artery, Common diagnostic imaging
Genetic Variation
Matrix Metalloproteinase 3 genetics
Promoter Regions, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1079-5642
- Volume :
- 20
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 10845878
- Full Text :
- https://doi.org/10.1161/01.atv.20.6.1600