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J Clin Endocrinol Metab. 2006 Apr;91(4):1438-45. Epub 2006 Jan 17.

Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study.

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  • 1Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.

Abstract

CONTEXT:

Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).

OBJECTIVE:

The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein lipase genotypes on triglycerides, HDL, and IHD.

DESIGN:

The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively.

SETTING:

The study was performed in the Danish general population (the Copenhagen City Heart Study).

PARTICIPANTS:

IHD was angina pectoris or myocardial infarction.

MAIN OUTCOME MEASURES:

Triglycerides, HDL, and IHD were the main outcome measures.

RESULTS:

Cross-sectionally, triglycerides varied by genotype with 1.27 mmol/liter in women and 1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD of 1.6 [95% confidence interval (CI), 1.2-2.3]; 291Ser and 447Ter did not change IHD risk. In the case-control study, combining the cohorts of IHD patients, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had an odds ratio for IHD of 1.5 (CI, 1.2-2.1). 291Ser and 447Ter did not change IHD risk. Stratified for apolipoprotein E genotype, the odds ratios for IHD in 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers were 2.6 (CI, 1.2-5.5) among epsilon32 individuals and 2.4 (CI, 1.4-4.1) among epsilon43 individuals.

CONCLUSIONS:

Genetic variation in lipoprotein lipase is associated with differences in plasma triglycerides greater than 1 mmol/liter and differences in HDL cholesterol greater than 0.5 mmol/liter. A 1.6-fold risk of IHD in 9Asn (with -93G) heterozygotes and homozygotes combined is influenced by apolipoprotein E genotype.

PMID:
16418216
[PubMed - indexed for MEDLINE]
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