TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study.
OBJECTIVE
Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cardiovascular and cerebrovascular complications. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with a central role in inflammation. Little is known of the relation of variations within the gene and risk of cardiovascular and cerebrovascular disease. We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study.


METHODS
Participants (N=6456) of the Rotterdam Study were included in the current study. Analyses of the relations of genotypes with the risk of myocardial infarction and stroke were performed according to Cox proportional-hazards methods. All analyses were adjusted for age, sex, conventional cardiovascular risk factors, and medical history.


RESULTS
We found no association with the risk of myocardial infarction. A significantly increased risk of stroke was found, associated with the T allele of the -509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to 1.48).


CONCLUSIONS
No association between the TGF-beta1 polymorphisms and myocardial infarction was observed; however, the -509 C/T and codon 10 Leu/Pro polymorphisms were associated with the risk of stroke.
Sie
Mark P S
MP
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Uitterlinden
André G
AG
Bos
Michiel J
MJ
Arp
Pascal P
PP
Breteler
Monique M B
MM
Koudstaal
Peter J
PJ
Pols
Huibert A P
HA
Hofman
Albert
A
van Duijn
Cornelia M
CM
Witteman
Jacqueline C M
JC
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009426:Netherlands; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1