Identification of the molecular basis of premature atherosclerosis in high penetrance pedigrees

Myocardial infarction is a leading cause of mortality and morbidity worldwide.
A number of well validated risk factors have been identified over the last
decades for cardiovascular disease (CVD) such as smoking, hypertension,
diabetes, obesity and dyslipidemias. In addition to these traditional factors,
several studies have confirmed that a family history of CVD is an independent
risk factor. However, the genetic basis for CVD is still not completely
understood. Myocardial infarctions in younger individuals have been associated
with substantially greater heritability. Thus, early-onset myocardial
infarction is a promising phenotype for mapping of genetic risk factors for
CVD4. At the Academic Medical Centre (AMC) in Amsterdam we have identified
pedigrees with several cases of early-onset CVD. It is tempting to speculate
that novel, high-penetrance mutation segregates in some of these pedigrees. We
will investigate these pedigrees.

We aim to identify sequence variations within pedigrees and determine how these
may result in CVD by studying the effect on cell phenotype.

Observational Pedigree Analysis

The burden for participants is a venipuncture and a skin biopsy of 1mm. The
risks are haematomas, a 1mm scar or bleeding. There is no direct benefit for
the participants. However in general more insight will be created in the
molecular basis of CVD.