Interaction between a common variant of the cholesteryl ester transfer protein gene and the apolipoprotein E polymorphism: effects on plasma lipids and lipoproteins in a cohort of 7-year-old children.
OBJECTIVE
Common variations in genes, such as apolipoprotein E (apo E) and cholesteryl ester transfer protein (CETP), are major determinants of plasma lipid and lipoprotein levels. As both apo E and CETP contribute to the reverse transport of cholesterol to the liver, the effects of variations at the CETP locus may very well interact with the apo E genotype.


RESULTS
As part of an ongoing study, the combined effects of the apo E genotype and heterogeneity at the CETP gene locus on plasma lipids and lipoproteins were studied in a birth cohort sample of 257 Dutch prepubescent boys and girls (aged 6.7-8.1 years). The children with an apo E2E3 genotype (carrying the epsilon 2 allele; arg158-->cys) had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) than those with an apo E4E3 (carrying the epsilon 4 allele; cys112-->arg) or apo E3E3 genotype (homozygous for the parent epsilon 3 allele). These associations were statistically significant in children who were homozygous (p = 0.004 for LDL; p = 0.002 for apo B) or heterozygous (p < 0.0001 for LDL and apo B) for the absence of the Taq-IB polymorphism at the CETP gene locus (B2 allele), but not in those homozygous for the presence of this variant (B1B1). The highest plasma high-density lipoprotein cholesterol (HDL-C) concentrations were observed in children with the CETP B2B2 genotype. The difference in HDL-C levels between the CETP genotype groups was statistically significant only in E2E3 carriers (p = 0.01). The LDL/HDL ratio was significantly lower in E2E3 carriers, but not when combined with a CETP B1B1 genotype.


CONCLUSIONS
These findings indicate that the apo E genotype and heterogeneity at the CETP gene locus have an additive and interactive influence on plasma lipid and lipoprotein levels in children.
Rump
P
P
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, Maastricht, The Netherlands. p.rump@medgen.azg.nl
Mensink
R P
RP
Hornstra
G
G
D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011336:Probability; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017678:Sex Distribution
D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins