The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (−77G→A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects

Ohta, Takao; Takata, Kazuhide; Katsuren, Keisuke; Fukuyama, Shigeru

doi:10.1016/j.bbalip.2004.01.008

Cited by 14 publications

(18 citation statements)

References 34 publications

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“…There is also a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in subjects with hypercholesterolemia but not in subjects with hypertriglyceridemia. In a previous study, Ohta et al [23] have found that the -77G > A variant affected serum HDL-C and ApoAI concentriations in hyperlipidemic subjects. The concentration of plasma HDL-C and ApoAI were significantly higher in A allele carriers than in A allele noncarriers.…”

Section: Discussionmentioning

confidence: 99%

“…It is unknown whether the ACAT-1 variants influence the ACAT1 activity. Ohta et al [23] have shown a relation between the -77G > A mutation and the plasma HDL concentration in hyperlipidemic subjects. It is likely that ACAT-1 gene with the mutation may not provide enough ACAT-1 protein for efficient catalysis of increased intracellular free cholesterol in the lipid-loaden status.…”

Section: Discussionmentioning

confidence: 99%

“…In lipid-loaden macrophages, however, it was confirmed that ACAT-1 depletion in macrophages is proatherogenic [15,16]. To explain these conflicts, the possible reasons might as follows: Firstly, in the ACAT-1 deletion modol, the ABCA1-mediated cholesterol efflux to protect macrophages from free cholesterol toxicity may be not sufficient in the status of completely lack of ACAT-1 [23]. While in our study, the ACAT-1 rs1044925 SNP did not affect the ACAT-1 activity greatly.…”

Section: Discussionmentioning

confidence: 99%

“…In a study of heterozygous subjects for ABCA1 mutations, the levels of cholesterol efflux account for 82% of the variation in HDL-C. Each 8% change in ABCA1-mediated efflux is predicted to be associated with a 0.1 mmol/L change in HDL-C [20]. In addition, previous studies have found the ACAT-1 gene polymorphisms affect serum HDL-C levels in endogenous hypertriglyceridemia [22], as well as hyperlipidemia [23]. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Yin

Aung

et al. 2012

Lipids Health Dis

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Yin

Aung

et al. 2012

Lipids Health Dis

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“…ACAT-1 is ubiquitously expressed in tissues except the intestine. A missense variant (R526G) and a variant in the 5' untranslated region (-77G-->A) have been identified recently [73]. In contrast, ACAT-2 is expressed mainly in the intestine in humans.…”

Section: Inhibitors Of Lipid Absorptionmentioning

confidence: 97%

Pharmacogenetics of Drugs Influencing Lipidic Metabolism

Ruano¹,

Fuentes²,

Pérez-Jiménez³

et al. 2005

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It is well recognized that most medications exhibit wide interindividual variability in their efficacy and toxicity. These differences may be due to genetic factors affecting the metabolism and action of these drugs, as well as to environmental factors. Genetic polymorphisms (SNPs and haplotypes) that may play a role in the differences in response to lipid lowering therapy have recently been identified, including genetic variants of apoproteins (apo AI, apo E, apo B), several enzymes (lipoprotein lipase, lecithin cholesterol acyl transferase, hepatic lipase), membrane transporters (ABCA1, ABCG5/8), and receptors (LDL cholesterol receptor). Clinical studies analysing relations between these genetic variants and the response to hypolipemiant drugs are exposed in this review.

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Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation

et al. 2019

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The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (−77G→A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects

Cited by 14 publications

References 34 publications

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

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

Pharmacogenetics of Drugs Influencing Lipidic Metabolism

Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation

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