UNIVERSITY NEWS
Genetic variation
of
clotting factors and the
myocardial infarction: study myocardial infarction risk
of
On 7 November 2000, C.J.M. Doggen was admitted to the degree ofdoctor of medicine at the University ofLeiden. A summary of the thesis is presented here.
known to be associated with coagulation factor levels in healthy persons. Polymorphisms remain unchanged after birth. If a certain genotype is associated with elevated activity or antigenic levels in healthy t~wo processes play a role in the persons, and the coagulation factor * development of a myocardial in- plays a causal role in the developfarction: atherosclerosis and throm- ment of a myocardial infarction, bosis. The formation of a thrombus then that genotype is expected to is crucial and it is therefore to be be more often present among paexpected that the risk of myocardial tients compared with control subinfarction is increased in the pre- jects. It is very unlikely that the cosence of elevated antigenic or activity levels of coagulation factors, agulation factors fibrinogen and facor in the presence of a mutation in tor VII play an aetiological role in one of these factors. The aim of this the development of myocardial indissertation is to clarify the role of farction. Polymorphisms which were coagulation factors in the develop- shown to be associated with activity ment of a myocardial infarction. and antigenic levels in healthy perThe Study of Myocardial Infarc- sons, were not associated with the tion Leiden is a case-control study risk of myocardial infarction. In the including 560 men who have had a case of factor VII the risk was even first myocardial infarction and 646 found to be decreased, rather than healthy subjects. It is not possible increased as was expected, especially to simply measure levels of coagu- in men below the age of 50 years. lation factors in patients, as these We could not confirm the association levels may be affected by athero- of a genetic variant in the plassclerosis, other cardiovascular risk minogen activator-i (PAI-1) gene factors and the event itself. Instead and levels. No conclusions could be ofmeasuring levels, we investigated drawn about the causality of PAI-I genetic polymorphisms which were itselffor myocardial infarction.
Nctherlands Heart Journal, Volume 9, Number 9, Decenber 2001
of
A mutation in the factor V gene (factor V Leiden) and the 202 1OA mutation in the prothrombin gene are important risk factors for venous thrombosis. We found that both mutations increase the risk of myocardial infarction about 1.5 fold. As it is likely that the risk is not only determined by genetic factors but also by other cardiovascular risk factors, we looked for interaction between the prothrombin mutations and major known risk factors. The risk was substantially increased when one of the major cardiovascular risk factors smoking, hypertension, diabetes mellitus or obesity was also present, with relative risks varying between 3-6. Given the high frequency of these mutations in the general population and the high prevalence of cardiovascular risk factors, this emphasises the need for prevention or treatment of these risk factors. Dr. C.J.M. Doggen. Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden.
405
Genetic variation
of
clotting factors and the
myocardial infarction: study myocardial infarction risk
of
On 7 November 2000, C.J.M. Doggen was admitted to the degree ofdoctor of medicine at the University ofLeiden. A summary of the thesis is presented here.
known to be associated with coagulation factor levels in healthy persons. Polymorphisms remain unchanged after birth. If a certain genotype is associated with elevated activity or antigenic levels in healthy t~wo processes play a role in the persons, and the coagulation factor * development of a myocardial in- plays a causal role in the developfarction: atherosclerosis and throm- ment of a myocardial infarction, bosis. The formation of a thrombus then that genotype is expected to is crucial and it is therefore to be be more often present among paexpected that the risk of myocardial tients compared with control subinfarction is increased in the pre- jects. It is very unlikely that the cosence of elevated antigenic or activity levels of coagulation factors, agulation factors fibrinogen and facor in the presence of a mutation in tor VII play an aetiological role in one of these factors. The aim of this the development of myocardial indissertation is to clarify the role of farction. Polymorphisms which were coagulation factors in the develop- shown to be associated with activity ment of a myocardial infarction. and antigenic levels in healthy perThe Study of Myocardial Infarc- sons, were not associated with the tion Leiden is a case-control study risk of myocardial infarction. In the including 560 men who have had a case of factor VII the risk was even first myocardial infarction and 646 found to be decreased, rather than healthy subjects. It is not possible increased as was expected, especially to simply measure levels of coagu- in men below the age of 50 years. lation factors in patients, as these We could not confirm the association levels may be affected by athero- of a genetic variant in the plassclerosis, other cardiovascular risk minogen activator-i (PAI-1) gene factors and the event itself. Instead and levels. No conclusions could be ofmeasuring levels, we investigated drawn about the causality of PAI-I genetic polymorphisms which were itselffor myocardial infarction.
Nctherlands Heart Journal, Volume 9, Number 9, Decenber 2001
of
A mutation in the factor V gene (factor V Leiden) and the 202 1OA mutation in the prothrombin gene are important risk factors for venous thrombosis. We found that both mutations increase the risk of myocardial infarction about 1.5 fold. As it is likely that the risk is not only determined by genetic factors but also by other cardiovascular risk factors, we looked for interaction between the prothrombin mutations and major known risk factors. The risk was substantially increased when one of the major cardiovascular risk factors smoking, hypertension, diabetes mellitus or obesity was also present, with relative risks varying between 3-6. Given the high frequency of these mutations in the general population and the high prevalence of cardiovascular risk factors, this emphasises the need for prevention or treatment of these risk factors. Dr. C.J.M. Doggen. Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden.
405
