APOE, CETP and LPL genes show strong association with lipid levels in Greek children.
OBJECTIVE
Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL-S447X), cholesterol ester transfer protein (CETP-Taq1B) apolipoprotein (APO) E (epsilon2, epsilon3, epsilon4), APOA5 (-1131C>T and S19W), APOA4 (S347T) and APOC3 (-482C>T; 1100C>T and 3238G>C) on lipoprotein levels children from the Gene-Diet Attica Investigation on childhood obesity (GENDAI).


RESULTS
The ten variants selected were genotyped in 882 Greek children, mean age: 11.2+/-0.7 years (418 females and 464 males). Genotypes were assessed using TaqMan technology. Significantly higher total cholesterol (TC) (p=0.0001) and low-density lipoprotein cholesterol (LDL-C) (p<0.0001) were observed in APOE epsilon4 carriers compared to epsilon3/epsilon3 homozygotes and epsilon2 carriers. The association of APOE genotype with TC and high-density lipoprotein cholesterol (HDL-C) ratio (p=0.0008) was further modulated by body mass index. Carriers of the CETP TaqIB B2 allele had significantly higher HDL-C (p<0.0001) and significantly lower TC: HDL-C ratio (p<0.0001) compared to B1/B1 individuals. No significant associations were observed between APOA4, APOA5 and APOC3 variants and serum lipids.


CONCLUSIONS
This study demonstrates that these common variants are associated with lipid levels in this healthy paediatric cohort, suggesting that even in these young children there may be potential in predicting their lifelong exposure to an adverse lipid profile.
Smart
M C
MC
Division of Cardiovascular Genetics, British Heart Foundation Laboratories, Department of Medicine, Royal Free and UCL Medical School, London, UK. m.smart@ucl.ac.uk
Dedoussis
G
G
Louizou
E
E
Yannakoulia
M
M
Drenos
F
F
Papoutsakis
C
C
Maniatis
N
N
Humphries
S E
SE
Talmud
P J
PJ
D053305:Apolipoprotein C-III / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006115:Greece; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013223:Statistics as Topic
D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002784:Cholesterol; C548261:LPL protein, human; D008071:Lipoprotein Lipase