Associations of Genetic Variants in ATP-Binding Cassette A1 and Cholesteryl Ester Transfer Protein and Differences in Lipoprotein Subclasses in the Multi-Ethnic Study of Atherosclerosis

Abstract

BACKGROUND ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. METHODS We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. RESULTS ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, −2505C/A AA, and −629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. CONCLUSIONS Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes.

Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

“…Additionally, our study reported a lack of association of this SNP with HDL concentrations and serum adipokine levels. This topic area has contradicting results in the literature, for example, Tsai et al [27] reported that A allele of rs1800777 polymorphism was associated with lower HDL concentrations. In another previous study, rs1800777 was associated with lower HDL cholesterol and carotid stenosis [28] too.…”

Genetic Determination of Plasma Cholesterol Efflux Capacity Is Gender-Specific and Independent of HDL-Cholesterol Levels

“…In good agreement with our data, earlier studies have reported that subjects carrying less frequent alleles of both the APOA1 c. -75 G>A or the ABCA1 pR219K SNPs displayed increased circulating levels of small HDL particles, which may account for the presently described improvement of plasma cholesterol efflux capacity. 13,32,33 The role of ApoAII in cholesterol efflux has been described using transgenic mice. In particular, serum from mice overexpressing human APOAII gene displayed a reduced capacity to stimulate cellular cholesterol efflux as compared with those from control mice.…”

“…13,16 However, the rs708272 SNP does not represent a functional regulatory site by itself but is a marker for other functional sites, such as the rs17231506 (CETP c.-1337 C>T) SNP. 17 Equally, it has been demonstrated that the rs1800588 (LIPC c.-514 C>T) SNP in the hepatic lipase gene promoter is associated with significant variations in plasma HDL2-C levels and HDL particle size with the T variant associated with higher HDL-C concentrations as a result of an increase in the large HDL subfraction.…”

“…12 The K219 allele is associated with higher plasma HDL-C and small HDL particle levels, and is proposed to be an antiatherogenic allele. 13 The functional rs5082 (APOAII c.-265 T>C) SNP has been shown to be associated with coronary artery disease risk.…”

Relacion De La Variante Rs1800777 Del Cholesteryl Ester Trasnfer Protein Variant Con La Masa Grasa, HDL Colesterol, en Sujetos Obesos Con Diabetes Mellitus Tipo 2

“…En un reciente estudio transversal multiétnico, Tsai y cols. (24) mostraron que el alelo A del polimorfismo rs1800777 estaba asociado con las concentraciones de HDL colesterol. En un estudio previo, el polimorfismo rs1800777 se asoció con mayor actividad de la proteína CETP y colesterol HDL más bajo, relacionándose también con estenosis carotidea y aumento de la presencia de calcio coronario (14).…”