Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

Marianne Benn

doi:10.1016/j.atherosclerosis.2009.01.004

Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

Marianne Benn

Ph.d.-studienævnet for Medicin

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

95 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Sep

Originalsprog	Engelsk
Tidsskrift	Atherosclerosis
Vol/bind	206
Udgave nummer	1
Sider (fra-til)	17-30
Antal sider	14
ISSN	0021-9150
DOI	https://doi.org/10.1016/j.atherosclerosis.2009.01.004
Status	Udgivet - 2009

Bibliografisk note

Keywords: Alleles; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Ischemia; Linkage Disequilibrium; Male; Polymorphism, Genetic; Risk Factors

Adgang til dokumentet

10.1016/j.atherosclerosis.2009.01.004

Citationsformater

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title = "Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review",

abstract = "Apolipoprotein B is a key component in lipid metabolism. Subendothelial retention of apolipoprotein B containing lipoproteins is a necessary initiating event in atherogenesis, and high plasma levels of apolipoprotein B is a risk factor for atherosclerosis, whereas low levels may provide protection. The present review examines, with focus on general population studies, apolipoprotein B levels as a predictor of ischemic cardiovascular disease, as well as the association of mutations and polymorphisms in APOB with plasma apolipoprotein B levels, and risk of ischemic cardiovascular disease. The studies can be summarized as follows: (1) apolipoprotein B predicts ischemic cardiovascular events in both genders, and is better than LDL cholesterol in this respect; (2) linkage disequilibrium structure in APOB is more complex than expected from HapMap data, because a minimal set of tag single nucleotide polymorphisms capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common polymorphisms are modest; (4) both mutations and polymorphisms are associated with LDL metabolism in vivo; (5) association of APOB mutations and polymorphisms with lipid and disease phenotype cannot be predicted in silico using evolutionary conservation or existing prediction programs; and finally, (6) except for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or ischemic stroke in the general population.",

author = "Marianne Benn",

note = "Keywords: Alleles; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Ischemia; Linkage Disequilibrium; Male; Polymorphism, Genetic; Risk Factors",

year = "2009",

doi = "10.1016/j.atherosclerosis.2009.01.004",

language = "English",

volume = "206",

pages = "17--30",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

AU - Benn, Marianne

N1 - Keywords: Alleles; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Ischemia; Linkage Disequilibrium; Male; Polymorphism, Genetic; Risk Factors

PY - 2009

Y1 - 2009

N2 - Apolipoprotein B is a key component in lipid metabolism. Subendothelial retention of apolipoprotein B containing lipoproteins is a necessary initiating event in atherogenesis, and high plasma levels of apolipoprotein B is a risk factor for atherosclerosis, whereas low levels may provide protection. The present review examines, with focus on general population studies, apolipoprotein B levels as a predictor of ischemic cardiovascular disease, as well as the association of mutations and polymorphisms in APOB with plasma apolipoprotein B levels, and risk of ischemic cardiovascular disease. The studies can be summarized as follows: (1) apolipoprotein B predicts ischemic cardiovascular events in both genders, and is better than LDL cholesterol in this respect; (2) linkage disequilibrium structure in APOB is more complex than expected from HapMap data, because a minimal set of tag single nucleotide polymorphisms capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common polymorphisms are modest; (4) both mutations and polymorphisms are associated with LDL metabolism in vivo; (5) association of APOB mutations and polymorphisms with lipid and disease phenotype cannot be predicted in silico using evolutionary conservation or existing prediction programs; and finally, (6) except for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or ischemic stroke in the general population.

AB - Apolipoprotein B is a key component in lipid metabolism. Subendothelial retention of apolipoprotein B containing lipoproteins is a necessary initiating event in atherogenesis, and high plasma levels of apolipoprotein B is a risk factor for atherosclerosis, whereas low levels may provide protection. The present review examines, with focus on general population studies, apolipoprotein B levels as a predictor of ischemic cardiovascular disease, as well as the association of mutations and polymorphisms in APOB with plasma apolipoprotein B levels, and risk of ischemic cardiovascular disease. The studies can be summarized as follows: (1) apolipoprotein B predicts ischemic cardiovascular events in both genders, and is better than LDL cholesterol in this respect; (2) linkage disequilibrium structure in APOB is more complex than expected from HapMap data, because a minimal set of tag single nucleotide polymorphisms capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common polymorphisms are modest; (4) both mutations and polymorphisms are associated with LDL metabolism in vivo; (5) association of APOB mutations and polymorphisms with lipid and disease phenotype cannot be predicted in silico using evolutionary conservation or existing prediction programs; and finally, (6) except for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or ischemic stroke in the general population.

U2 - 10.1016/j.atherosclerosis.2009.01.004

DO - 10.1016/j.atherosclerosis.2009.01.004

M3 - Journal article

C2 - 19200547

SN - 0021-9150

VL - 206

SP - 17

EP - 30

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

ER -