A protective role of a cholesteryl ester transfer protein gene variant towards ischaemic stroke in Sardinians

J Intern Med. 2007 Nov;262(5):555-61. doi: 10.1111/j.1365-2796.2007.01845.x.

Abstract

Objectives: Cholesteryl ester transfer protein (CETP) plays a key role in the metabolism of high-density lipoprotein (HDL), a strong, inverse, independent risk factor for cardiovascular disease. We sought to investigate the relationship between a common variant of CETP gene, the Taq1 B polymorphism, that has been previously associated with CETP blood concentrations, and the risk of ischaemic stroke in a genetically homogenous population from the Sardinia island, Italy. This population has been previously shown to be a highly conservative sample.

Design: A total of 215 cases of ischaemic stroke and 236 controls were selected and characterized for the CETP Taq1 B polymorphism. Allele and genotype frequencies were compared amongst cases and controls.

Results: Age, hypertension and hypercholesterolaemia were independent risk factors for stroke in this cohort. We found that presence of the CETP Taq1 B2 allele was associated with a significantly decreased risk of ischaemic stroke when assuming a recessive mode of inheritance (OR 0.55, 95% CI = 0.34-0.90, P = 0.017). This result was confirmed by multivariate analysis, after adjustment for age, presence of hypertension and hypercholesterolaemia (OR 0.53, 95% CI = 0.32-0.88, P = 0.014). By performing separate analysis for gender we found that the effect was present in females but not in males, with a significant sex-CETP gene variant interaction for both recessive (P = 0.005) and additive (P = 0.029) modes of inheritance.

Conclusions: Our data suggest that the Taq1 B2 allelic variant of the CETP gene may be associated, as a protective factor, with occurrence of ischaemic stroke. Further studies are needed to further elucidate the clinical implications of our finding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Brain Ischemia / epidemiology
  • Brain Ischemia / genetics
  • Case-Control Studies
  • Cholesterol Ester Transfer Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Risk Factors
  • Sex Distribution
  • Stroke / epidemiology
  • Stroke / genetics*

Substances

  • CETP protein, human
  • Cholesterol Ester Transfer Proteins