Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease: A Meta-Analysis

Wittrup, Hans H.; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.

doi:10.1161/01.cir.99.22.2901

Cited by 344Lipid metabolism and disordersLipoproteins and Cardiovascular HealthParaoxonase enzyme and polymorphisms

Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease: A Meta-Analysis

Wittrup, Hans H., Tybjærg-Hansen, Anne, Nordestgaard, Børge G.·1999·Circulation

DOI 10.1161/01.cir.99.22.2901

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Abstract

Background —We assessed in meta-analyses the effect of the Gly188Glu, Asp9Asn, Asn291Ser, and Ser447Ter substitutions in lipoprotein lipase in the heterozygous state on lipid metabolism and risk of ischemic heart disease (same order used below). Methods and Results —In 29 separate studies, 20 903 white subjects were screened for ≥1 of these substitutions; each meta-analysis included only some of these individuals. In population-based studies, heterozygote frequencies ranged from 0.04% to 0.2%, 2% to 4%, 1% to 7%, and 17% to 22% for the respective substitutions. Postheparin plasma lipoprotein lipase activity decreased 53% (95% CI, 31% to 75%) (only 1 study), 30% (22% to 37%), and 22% (8% to 35%) and was unchanged at 4% (−10% to 19%), respectively. Plasma triglycerides increased 78% (95% CI, 64% to 92%), 20% (9% to 33%), and 31% (20% to 43%) and decreased 8% (4% to 11%), respectively. HDL cholesterol decreased 0.25 mmol/L (0.18 to 0.32), 0.08 mmol/L (0.04 to 0.12), and 0.12 mmol/L (0.10 to 0.15) and increased 0.04 mmol/L (0.02 to 0.06), respectively. Odds ratios for ischemic heart disease were 4.9 (95% CI, 1.2 to 20) (only 1 study), 1.4 (0.8 to 2.4), 1.2 (0.9 to 1.5), and 0.8 (0.7 to 1.0), respectively. Subgroup analysis indicated that women with the Asn291Ser substitution may have an increased risk of ischemic heart disease. Conclusions —These meta-analyses suggest that compared with noncarriers, carriers of the Gly188Glu, Asp9Asn, and Asn291Ser substitutions have an atherogenic lipoprotein profile, whereas carriers of the Ser447Ter substitution have a protective lipoprotein profile. Accordingly, risk of ischemic heart disease in heterozygous carriers is increased for Gly188Glu carriers; at most, the increase is borderline for Asp9Asn and Asn291Ser carriers; and risk is possibly decreased for Ser447Ter carriers.

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Loss-of-function mutations in LPL are associated with increased plasma TG levels and risk of ASCVD.
“LOF mutations in LPL are also associated with increased plasma TG levels and risk of ASCVD”
From The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk (2019) · cites this paper as [128]
The Plasma Triglycerides and Postheparin Plasma Lipoprotein Lipase Activity sections report that three LPL substitutions associated with reduced enzyme activity also increased triglycerides. The Risk of Ischemic Heart Disease and Discussion sections report increased risk for Gly188Glu carriers, but say any increase for Asp9Asn and Asn291Ser carriers was borderline at most. The claim overgeneralizes the cardiovascular-risk association across loss-of-function mutations. (LLM, conf=0.88)
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Authors: Wittrup, H. H., Tybjærg-Hansen, A., & Nordestgaard, B. G.
Affiliations: Herlev Hospital (DK)
From the Department of Clinical Biochemistry, Herlev University Hospital (H.H.W., A.T.-H.), Herlev, Denmark, and Department of Clinical Biochemistry, Glostrup University Hospital (B.G.N.), Glostrup, Denmark.
ORCID: Nordestgaard, Børge G.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999-06-08
Volume: 99
Issue: 22
Pages: 2901-2907
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.99.22.2901
OpenAlex: W2011468836
Cited by: 344
References: 45
Citations by year: 2026: 2 · 2025: 8 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 17 · 2015: 13 · 2014: 11 · 2013: 12 · 2012: 11
FWCI: 3.64
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Funders: Hjerteforeningen
Sundhed og Sygdom, Det Frie Forskningsråd
Medical Research Council
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords: lipoprotein lipase, heterozygous carriers, ischemic heart disease risk, plasma triglycerides, HDL cholesterol, lipid metabolism, sex differences, genetic susceptibility
MeSH terms: Apolipoproteins B, Cholesterol, Cross-Sectional Studies, Female, Heparin, Humans, Lipids, Lipoprotein Lipase, Lipoproteins, Cholesterol, HDL, Male, Mutation, Risk Factors, Triglycerides, Case-Control Studies, Apolipoprotein A-I, Myocardial Ischemia

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Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease: A Meta-Analysis

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