Common sequence variant in lipoprotein lipase gene conferring triglyceride response to fibrate treatment

Pharmacogenomics. 2009 Feb;10(2):267-76. doi: 10.2217/14622416.10.2.267.

Abstract

Aims: Little is known about whether the variations in the lipoprotein lipase (LPL) and apolipoprotein gene cluster (APOA1/C3/A5) confer appreciable triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.

Materials & methods: We investigated whether variations in these genes confer a triglyceride lowering response after fibrate treatment among 145 patients with hypertriglyceridemia receiving 6 months of fibrate treatment.

Results: Overall triglycerides decreased from 746.2 mg/dl to 465.9 mg/dl and the mean percentage of triglyceride lowering was 50.7 +/- 38.6%. A total of two polymorphisms, LPL IVS8 +483T>G and APOA1 +2169G>C, were associated with a significant percentage of triglyceride lowering. Common haplotype effects of LPL on the triglyceride lowering percentage were significant (p = 0.002) and the percentage of variance explained by the LPL haplotype was 7.5%. One common LPL haplotype encompassing three polymorphisms was associated with a -45.40% change (p < 0.001) and risk of a 5.9-fold risk for developing a poor response (95% confidence interval: 1.11-31, p = 0.037), compared with the most frequent LPL haplotype.

Conclusion: Our results indicate that the LPL gene variant may cause triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins / genetics
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Clofibrate / therapeutic use*
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy
  • Hypertriglyceridemia / enzymology
  • Hypertriglyceridemia / genetics*
  • Hypolipidemic Agents / therapeutic use
  • Introns
  • Lipoprotein Lipase / genetics*
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, LDL / blood
  • Male
  • Multigene Family
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Triglycerides / metabolism*

Substances

  • Apolipoproteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Lipoproteins, LDL
  • Triglycerides
  • Cholesterol
  • Lipoprotein Lipase
  • Clofibrate