Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.
Many epidemiologic studies from Europe and North America have found that when plasma levels of lipoprotein (a) exceed 0.20 g/L, there is a significantly higher risk of coronary and cerebrovascular atherosclerosis.
In summary, by showing that Lp(a) concentrations and apo(a) apparent size are highly correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene, we provide a DNA marker for this atherosclerosis risk factor as well as an important insight into the genetic mechanism regulating Lp(a) levels.
Elevated plasma levels of the lipoprotein Lp(a) are associated with increased risk for atherosclerosis and its manifestations, myocardial infarction, stroke and restenosis (for reviews, see refs 1-3).
Elevated plasma levels of the lipoprotein Lp(a) are associated with increased risk for atherosclerosis and its manifestations, myocardial infarction, stroke and restenosis (for reviews, see refs 1-3).
The interest in Lp(a) lipoprotein [Lp(a)] has increased dramatically during the last few years due to the documented strong association between high Lp(a) levels and early atherosclerosis and its sequelae and the probable additional thrombogenic effect of inherited high Lp(a) levels.
Elevated blood levels of apolipoprotein(a), the component of lipoprotein(a) that distinguishes it from low density lipoprotein, are a major risk factor for atherosclerosis.
Transgenic mice expressing human apolipoprotein(a) develop aortic lesions resembling the early stages of human atherosclerosis after 3.5 months on a high fat diet.
The exceptionally strong independent association found between Lp(a) lipoprotein [Lp(a)] levels and atherosclerotic disorders indicate that Lp(a) is a factor of considerable importance in the pathogenesis of atherosclerosis.
Genetic dyslipidemias can be identified in over 75% of CAD patients and include the atherosclerosis susceptibility trait (low density lipoprotein [LDL] pattern B), hyperapobetalipoproteinemia, lipoprotein (a), apo E isoforms, and lipoprotein susceptibility to oxidative damage.
In hyperlipidemia and, in particular, elevated lipoprotein (a) [Lp(a)] levels there appears to be pronounced linkage between the development and progression of atherosclerosis.
The former was only present in 2 of the 100 subjects studied, was associated with a lysine-binding defective lipoprotein(a) [Lp(a)], low plasma levels of Lp(a), and no evidence of atherosclerotic cardiovascular disease (ASCVD).
While our findings suggest that Lp(a) plasma levels and apo(a) isoforms are not factors associated with longevity or disability, we cannot exclude that the low incidence of other major risk factors for atherosclerosis in our free-living octo-nonagenarians hampered the full expression of the lipoprotein(a) atherogenic potential, and thus allowed the achievement of a very old age in a good healthy status, even in carriers of high Lp(a) levels or small apo(a) isoforms.