Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks.
PLoS One
; 9(12): e114618, 2014.
Article
in En
| MEDLINE
| ID: mdl-25502880
ABSTRACT
Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triglycerides
/
Polymorphism, Single Nucleotide
/
Black People
/
White People
/
Genetic Association Studies
/
Cholesterol, HDL
/
Cholesterol, LDL
Type of study:
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
America do norte
Language:
En
Journal:
PLoS One
Year:
2014
Document type:
Article