title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  The study was performed in the Danish general population (the Copenhagen City Heart Study).
  
  
  METHODS
  IHD was angina pectoris or myocardial infarction.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wittrup
authors.forename: Rolf V
authors.initials: RV
authors.lastname: Andersen
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: Gorm B
authors.initials: GB
authors.lastname: Jensen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000235:genetics; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics*; D011446:Prospective Studies; D012306:Risk; D014280:Triglycerides / Q000097:blood*
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; D004247:DNA; D008071:Lipoprotein Lipase