Genetic variation in MDR1, LPL and eNOS genes and the response to atorvastatin treatment in ischemic stroke

Hum Genet. 2012 Nov;131(11):1775-81. doi: 10.1007/s00439-012-1202-2. Epub 2012 Jul 19.

Abstract

Statins reduce the risk of cardiovascular events by lowering the blood cholesterol. Many genes involved in the pharmacodynamic pathway of statins have been part of pharmacogenetic research in patients with hypercholesterolemia, with an emphasis on genes involved in the cholesterol pathway. The present study was carried out with an aim to evaluate the association between the genetic variants of lipoprotein lipase gene [HindIII (+/+)/HindIII (-/-)], multiple drug resistance gene (C3435T) and endothelial nitric oxide synthase gene (4a/4b) with clinical outcome including an increased risk of recurrent stroke or death in ischemic stroke patients on atorvastatin therapy. 525 stroke patients and 500 healthy controls were involved in the study. Follow-up telephone interviews were conducted with patients post-event to determine stroke outcome. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. A significant association of MDR1 and LPL gene variants with bad outcome in stroke patients on atorvastatin therapy was found. However, there was no significant association of 27 bp VNTR polymorphism of eNOS gene with outcome. MDR analysis was carried out to analyze gene-gene interaction involving these gene variants contributing to clinical outcome of patients on stratin therapy but no significant interaction between these variants was observed. In conclusion the individuals with HindIII (-/-) genotype of LPL and CC genotype of MDR1 gene would benefit more from atorvastatin therapy.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Ischemia / drug therapy
  • Ischemia / genetics*
  • Lipoprotein Lipase / genetics*
  • Male
  • Middle Aged
  • Minisatellite Repeats
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Pyrroles / therapeutic use*
  • Risk Factors
  • Stroke / drug therapy
  • Stroke / genetics*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticholesteremic Agents
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • LPL protein, human
  • Lipoprotein Lipase