Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response

Clin Chim Acta. 2013 Feb 18:417:8-11. doi: 10.1016/j.cca.2012.11.028. Epub 2012 Dec 13.

Abstract

Objective: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response.

Methods: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology.

Results: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p=0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p=0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (>160mg/dL). After atorvastatin treatment (10mg/day/4weeks), LIPC -514T allele was positively associated with LDL cholesterol reduction.

Conclusion: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC -514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / complications*
  • Atorvastatin
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics*
  • Dyslipidemias / metabolism
  • Female
  • Genotype
  • Heptanoic Acids / pharmacokinetics
  • Heptanoic Acids / pharmacology*
  • Heptanoic Acids / therapeutic use
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Pyrroles / pharmacokinetics
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Treatment Outcome

Substances

  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin