title: The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population.
abstract: BACKGROUND
  Apolipoprotein E (ApoE) locus has consistently shown a significant association with low-density lipoprotein cholesterol (LDL-C). However, its impact on high-density lipoprotein cholesterol (HDL-C) has been highly controversial suggesting that it may be context-dependent. We examined the gene-gene interaction between the common ApoE and the CETP polymorphisms in determining HDL-C concentrations in men and women from the general population.
  
  
  METHODS
  550 unrelated Caucasian subjects were randomly selected from a Mediterranean Region in Spain. Plasma lipids, anthropometric, clinical and lifestyle variables were measured. Common ApoE and CETP-TaqIB polymorphisms were determined.
  
  
  RESULTS
  We have found a gene-gene interaction between and ApoE and the CETP loci in determining HDL-C concentrations. Thus, after adjustment for gender, age, body mass index, tobacco smoking, alcohol consumption, physical exercise and medication, carriers of the E4 allele had lower HDL-C concentrations [mean and (standard error): 40.1 (2.6) mg/dL] than E2 subjects [47.7 (3.2) mg/dL; p=0.019], and even lower than those of the E3 subjects [44.7 (1.4) mg/dL; p=0.042], only if they had the B1B1 genotype. However, mean HDL-C concentrations were higher among those with E4 allele carrying the B2 allele at the CETP gene locus [50.5 (2.3) mg/dL], and lower among E2 subjects carrying the B2 allele [45.5 (2.6) mg/dL]. This interaction was observed in both men and women. This gene-gene interaction remained statistically significant even after additional adjustment for triglycerides.
  
  
  CONCLUSIONS
  The effect of the ApoE polymorphism on HDL-C concentrations depends on the CETP polymorphism, explaining some of the controversial results previously reported for this polymorphism.
authors.affiliation: Department of Preventive Medicine and Public Health, Genetic and Molecular Epidemiology Unit, School of Medicine, University of Valencia, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain. sorli@uv.es
authors.forename: José V
authors.initials: JV
authors.lastname: Sorlí
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Francesc
authors.initials: F
authors.lastname: Francés
authors.forename: Judith B
authors.initials: JB
authors.lastname: Ramírez
authors.forename: José I
authors.initials: JI
authors.lastname: González
authors.forename: Marisa
authors.initials: M
authors.lastname: Guillén
authors.forename: Olga
authors.initials: O
authors.lastname: Portolés
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D013030:Spain; D044465:White People / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008055:Lipids