© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects
From the Department of Experimental and Clinical Medicine (A.G., C.I., C. Carallo, P.L.M.), Atherosclerosis Unit, University of Catanzaro "Magna Græcia," Catanzaro, Italy; the Institute of Biochemistry and Molecular Biology (C.M.), University of Teramo, Teramo, Italy; and the Clinical Biochemistry Laboratory (G.F.), IRCCS Bambino Gesù, and the Department of Internal Medicine (L.L., S.B., R.M., C. Cortese), University of Tor Vergata, Rome, Italy.
Correspondence to Prof Claudio Cortese, Dipartimento di Medicina Interna, Università di Tor Vergata, Via di Tor Vergata 135, 00133 Roma, Italy. E-mail cortese{at}uniroma2.it
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 µm [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/cm2 [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.
Key Words: carotid arteries • atherosclerosis • ultrasonics • metalloproteinases • polymerase chain reaction
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