The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population.
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.
Sorlí
José V
JV
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
Corella
Dolores
D
Francés
Francesc
F
Ramírez
Judith B
JB
González
José I
JI
Guillén
Marisa
M
Portolés
Olga
O
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
D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008055:Lipids