(Circulation. 1999;99:2901-2907.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease
A Meta-Analysis
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.
Correspondence to Hans H. Wittrup, MD, PhD, Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark. E-mail hans{at}wittrup.net
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.
Key Words: lipoproteins • genetics • cholesterol • heart diseases • meta-analysis • enzymes
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