Published online before print June 5, 2003, doi: 10.1161/01.STR.0000076013.00240.B0
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(Stroke. 2003;34:1623.)
© 2003 American Heart Association, Inc.
Original Contributions |
Polymorphism in the Promoter Region of the Insulin-like Growth Factor I Gene Is Related to Carotid Intima-Media Thickness and Aortic Pulse Wave Velocity in Subjects With Hypertension
From the Departments of Epidemiology and Biostatistics (A.F.C.S., J.M.V., A.H., H.A.P.P., J.C.M.W., C.M. van D.), Internal Medicine (A.F.C.S., J.A.M.J.L.J., J.D., S.W.J.L., H.A.P.P.), and Clinical Genetics (B.A.O.), Erasmus Medical Center Rotterdam, Rotterdam, Netherlands.
Correspondence to Professor Cornelia M. van Duijn, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands. E-mail c.vanduijn{at}erasmusmc.nl
Background and Purpose— Low circulating levels of insulin-like growth factor I (IGF-I) have been associated with an increased risk for atherosclerosis. Absence of the 192-bp (wild-type) allele in the promoter region of the IGF-I gene has been associated with low circulating IGF-I levels. We examined the role of this polymorphism in relation to blood pressure and 2 early markers of atherosclerosis: carotid intima-media thickness (IMT) and aortic pulse wave velocity (PWV).
Methods— A total of 5132 subjects of the Rotterdam Study, aged 55 to 75 years, were included in this study. In 3769 subjects who did not use blood pressure–lowering medication, the association between the IGF-I polymorphism and blood pressure was examined. In the total population, and in 3484 normotensive subjects, 1648 hypertensive and 462 untreated hypertensive subjects, the association between this polymorphism and IMT and PWV was examined.
Results— Mean systolic and diastolic blood pressure did not differ between genotypes. In hypertensive subjects IMT was significantly increased in noncarriers of the 192-bp allele (0.83 mm) compared with heterozygous or homozygous carriers (0.80 mm) (P=0.04). PWV was also significantly higher in hypertensive subjects who were noncarriers of the 192-bp allele (14.3 m/s) compared with heterozygous (14.1 m/s) or homozygous carriers (13.7 m/s) (P=0.02). Findings were more pronounced in hypertensive subjects without medication use. In normotensive subjects, no association between this polymorphism, IMT, and PWV was observed.
Conclusions— Our study suggests that hypertensive subjects who have low IGF-I levels because of a genetic polymorphism in the IGF-I gene are at increased risk of developing atherosclerosis.
Key Words: atherosclerosis • cardiovascular diseases • genetics • growth factors • hypertension • risk factors
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