title: Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response.
abstract: BACKGROUND
  Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL.
  
  
  METHODS
  Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls.
  
  
  RESULTS
  The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively).
  
  
  CONCLUSIONS
  A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects.
authors.affiliation: Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.forename: Marta
authors.initials: M
authors.lastname: Artieda
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonzalvo
authors.forename: Erardo
authors.initials: E
authors.lastname: Meriño-Ibarra
authors.forename: Rosa
authors.initials: R
authors.lastname: Arístegui
authors.forename: Alberto
authors.initials: A
authors.lastname: Gañán
authors.forename: Cristina
authors.initials: C
authors.lastname: Díaz
authors.forename: Josep María
authors.initials: JM
authors.lastname: Sol
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocoví
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001629:Bezafibrate / Q000627:therapeutic use; D003596:Cytosine; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008049:Lipase / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use; D012016:Reference Values; D013941:Thymine
chemical_list: D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; C504173:LIPC protein, human; D008055:Lipids; D008074:Lipoproteins; D011758:Pyrroles; D003596:Cytosine; D000069059:Atorvastatin; D008049:Lipase; D013941:Thymine; D001629:Bezafibrate