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.

HH Wittrup, RV Andersen, Anne Tybjærg-Hansen, Gorm Boje Jensen, BG Nordestgaard

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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.
OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind91
Udgave nummer4
Sider (fra-til)1438-45
ISSN0021-972X
StatusUdgivet - 2006

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