title: Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on serum high-density lipoprotein cholesterol levels.
abstract: OBJECTIVE
  Polymorphisms in the hepatic lipase (LIPC -514C > T) and cholesteryl ester transfer protein (CETP I405V) genes affect high-density lipoprotein cholesterol (HDL-c) levels, but their relationship with cardiovascular disease and their combined effect is unclear. The objectives of the current study were to characterize the effect of the hepatic lipase variant, and its interaction with the CETP variant, in terms of cholesterol levels, atherosclerosis, and risk of myocardial infarction (MI).
  
  
  METHODS
  The study was conducted in the Rotterdam Study, a large single-center prospective cohort study in people aged 55 yr and older. Lipid levels were analyzed using linear regression models, and risk of MI was assessed with Cox proportional hazards models.
  
  
  RESULTS
  The hepatic lipase variant was associated with an increase in serum HDL-c levels of 0.11 mmol/liter in both genders, whereas an increased risk of MI was observed only in men [hazard ratio, 1.32 (95% confidence interval, 1.05-1.66) for CT vs. CC and 1.75 (95% confidence interval, 1.39-2.20) for TT vs. CC]. This effect was independent of serum HDL-c. LIPC -514C > T interacted with CETP I405V with respect to serum HDL-c concentrations. Those homozygous for both mutations saw a marked elevation in HDL-c levels (0.29 mmol/liter, P(interaction) = 0.05). These increased HDL-c levels, however, were not inversely associated with atherosclerosis or MI risk.
  
  
  CONCLUSIONS
  LIPC genotype affects HDL-c levels and risk of MI in males. The interaction of this variant with CETP on HDL-c levels helps elucidate the underlying mechanisms and suggests that the beneficial effects of CETP inhibition may vary in particular subgroups.
authors: Genetic Epidemiology Unit, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors: Aaron
authors: A
authors: Isaacs
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Albert
authors: A
authors: Hofman
authors: Eric J G
authors: EJ
authors: Sijbrands
authors: Fakhredin A
authors: FA
authors: Sayed-Tabatabaei
authors: Olaf H
authors: OH
authors: Klungel
authors: Anke-Hilse
authors: AH
authors: Maitland-van der Zee
authors: Bruno H Ch
authors: BH
authors: Stricker
authors: Ben A
authors: BA
authors: Oostra
authors: Jacqueline C M
authors: JC
authors: Witteman
authors: Cornelia M
authors: CM
authors: van Duijn
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D053480:Cholesterol Ester Transfer Proteins; C504173:LIPC protein, human; D008075:Lipoproteins, HDL; D008049:Lipase