Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects

Abstract

BackgroundAcyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects.MethodsA total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThere was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P < 0.05-0.01), the C allele carriers had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. The association of genotypes and serum HDL-C and ApoAI levels in hyperlipidemia was found mainly in the male subjects with hypercholesterolemia but not in those with hypertriglyceridemia. There were no significant differences in serum lipid levels between the AA and AC/CC genotypes in the normolipidemic subjects.ConclusionsThe present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.

Effects ofω-3 Polyunsaturated Fatty Acids on Plasma Proteome in Rett Syndrome

“…At the same time, ω -3 PUFAs show a direct regulation on gene expression vianuclear receptors and transcription factors, which are in turn modulated by cytoplasmic lipid binding proteins transporting these fatty acids into the nucleus. Regulation of ω -3 PUFAs on gene expression could explain the altered protein expression that we reported on the RTT plasma proteome and is in line with previous findings in adult smokers following a short course (i.e., 5 weeks) of ω -3 PUFAs enriched diet [12]. In this latter study, proteins related to the antioxidant, anti-inflammatory, and antiatherosclerotic properties of HDL were upregulated, in contrast with down-regulation of complement activation and APR proteins.…”

Association between Single Nucleotide Polymorphism rs1044925 and the Risk of Coronary Artery Disease and Ischemic Stroke

“…However, plasma concentrations of HDL-C and ApoAI in subjects with the 77G-A variant were significantly higher than in hyperlipidemic subjects without the variant. In a previous study, we also showed that rs1044925 was associated with increased serum HDL-C only in hyperlipidemic subjects [24]. These data suggest that the ACAT-1 variants may be associated with reduced ACAT-1 protein expression and influence cellular cholesterol efflux on hyperlipidemia, thereby playing an important role in atherosclerosis progression.…”

“…Genomic DNA was isolated from peripheral blood leukocytes using the phenol-chloroform method [24,27]. Genotyping of rs1044925 was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).…”

Association of the SPTLC3 rs364585 polymorphism and serum lipid profiles in two Chinese ethnic groups

“…Genomic DNA was isolated from peripheral blood leukocytes using the phenol-chloroform method [31, 32]. The extracted DNA was stored at 4 °C until analysis.…”