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.
Highlights
Cholesterol is present in tissues and in plasma lipoproteins either as free cholesterol or cholesteryl esters
When hyperlipidemia was divided into hypercholesterolemia and hypertriglyceridemia, we found that the levels of high-density lipoprotein cholesterol (HDL-C) and ApoAI in hypercholesterolemia but not in hypertriglyceridemia were different between the AA and AC/CC genotypes in males but not in females (Table 4), the subjects with AC/CC genotype had higher serum HDL-C and ApoAI levels than the subjects with AA genotype
In the present study, we showed that the levels of HDLC, low-density lipoprotein cholesterol (LDL-C), ApoAI and ApoB were higher in subjects with hyperlipidemia than in subjects with normolipidemia besides serum total cholesterol (TC) and TG levels, whereas the ratio of ApoAI to ApoB was lower in subjects with hyperlipidemia than in subjects with normolipidemia
Summary
Cholesterol is present in tissues and in plasma lipoproteins either as free cholesterol or cholesteryl esters. The extent of cholesterol efflux is highly correlated with serum ApoAI and high-density lipoprotein cholesterol (HDL-C) concentrations [19,20,21]. Based on the above concept, we hypothesize that the ACAT-1 rs1044925 SNP might influence the cellular cholesterol efflux and regulate the concentration of serum HDL-C and ApoAI in the hyperlipidemic subjects. The aim of the present research was to determine whether the ACAT-1 rs1044925 SNP affect the concentration of serum lipid levels associated with the cellular cholesterol efflux in the hyperlipidemic subjects. 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
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