Resequencing of the CETP gene in American whites and African blacks: Association of rare and common variants with HDL-cholesterol levels.
Metabolism
; 65(1): 36-47, 2016 Jan.
Article
in En
| MEDLINE
| ID: mdl-26683795
ABSTRACT
BACKGROUND:
Cholesteryl ester transfer protein (CETP) plays a crucial role in lipid metabolism. Associations of common CETP variants with variation in plasma lipid levels, and/or CETP mass/activity have been extensively studied and well-documented; however, the effects of uncommon/rare CETP variants on plasma lipid profile remain undefined. Hence, resequencing of the gene in extreme phenotypes and follow-up rare-variant association analyses are essential to fill this gap.OBJECTIVE:
To identify common and uncommon/rare variants in the CETP gene by resequencing the entire gene and test the effects of both common and uncommon/rare CETP variants on plasma lipid traits in two genetically distinct populations. METHODS ANDRESULTS:
The entire CETP gene plus flanking regions were resequenced in 190 individuals comprising 95 non-Hispanic whites (NHWs) and 95 African blacks with extreme HDL-C levels. A total of 279 sequence variants were identified, of which 25 were novel. Selected variants were genotyped in the entire samples of 623 NHWs and 788 African blacks and 184 QC-passed variants were tested in relation to plasma lipid traits by using gene-based, single-site, haplotype and rare variant association analyses (SKAT-O). Two novel and independent associations of rs1968905 and rs289740 with HDL-C were identified in African blacks. Using SKAT-O analysis, we also identified rare variants with minor allele frequency <0.01 to be associated with HDL-C in both NHWs (P=0.024) and African blacks (P=0.009).CONCLUSIONS:
Our results point out that in addition to the common CETP variants, rare genetic variants in the CETP gene also contribute to the phenotypic variation of HDL-C in the general population.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Black People
/
White People
/
Cholesterol Ester Transfer Proteins
/
Cholesterol, HDL
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Metabolism
Year:
2016
Document type:
Article