Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

TY - JOUR

T1 - Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

AU - Nordestgaard, Børge G

AU - Tybjærg-Hansen, Anne

PY - 2011/4

Y1 - 2011/4

N2 - Purpose of Review To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease. Recent Findings: Evidence for concordance or discordance with cardiovascular disease risk has come from Mendelian randomization studies, whereas indirect evidence also has emerged from genome-wide and candidate gene association studies. The major limitations of studies of genetic variation and concordance or discordance with cardiovascular disease are pleiotropic effects of the variants studied, and/or lack of sufficient statistical power of the majority of studies to firmly demonstrate a positive association, or even more difficult, to exclude an association. Summary: New and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), and triglyceride-rich lipoproteins are concordant with both the magnitude and direction of the expected risk of cardiovascular disease, whereas this is unclear for HDL cholesterol. The data are compatible with cardiovascular disease causality for the three former lipoprotein classes, but not for HDL cholesterol.

AB - Purpose of Review To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease. Recent Findings: Evidence for concordance or discordance with cardiovascular disease risk has come from Mendelian randomization studies, whereas indirect evidence also has emerged from genome-wide and candidate gene association studies. The major limitations of studies of genetic variation and concordance or discordance with cardiovascular disease are pleiotropic effects of the variants studied, and/or lack of sufficient statistical power of the majority of studies to firmly demonstrate a positive association, or even more difficult, to exclude an association. Summary: New and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), and triglyceride-rich lipoproteins are concordant with both the magnitude and direction of the expected risk of cardiovascular disease, whereas this is unclear for HDL cholesterol. The data are compatible with cardiovascular disease causality for the three former lipoprotein classes, but not for HDL cholesterol.

U2 - 10.1097/mol.0b013e32834477d2

DO - 10.1097/mol.0b013e32834477d2

M3 - Journal article

SN - 0957-9672

VL - 22

SP - 113

EP - 122

JO - Current Opinion in Lipidology

JF - Current Opinion in Lipidology

IS - 2

ER -