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

Dong-Feng Wu,Rui-Xing Yin,Wu-Xian Chen,Xiao-Li Cao

doi:10.3390/ijms15033546

Abstract

The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls (p = 0.015) and borderline different between the IS patients and controls (p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.

Highlights

Cholesterol is present in the membranes of all mammalian cells and is needed for their growth and viability
The average body mass index (BMI), diastolic blood pressure, pulse pressure, and serum triglyceride (TG) levels were significantly higher and serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Apo AI, ApoAI/ApoB ratio and the percentages of subjects who consumed alcohol were significantly lower in the coronary artery disease (CAD) and ischemic stroke (IS) patients than in the controls
We showed that the frequencies of the AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS

Summary

Introduction

Cholesterol is present in the membranes of all mammalian cells and is needed for their growth and viability. Excess cellular cholesterol is stored as cholesteryl esters (CEs). CEs are present only in low levels, mainly as cytoplasmic lipid droplets. Chronic accumulation of CE in macrophages causes these cells to appear foamy and is a hallmark of early-stage atherosclerosis [1]. The formation of CEs is catalyzed by the enzyme acyl-coenzyme A (CoA):cholesterol acyltransferase (ACAT) [2]. There are two isozymes of ACAT, ACAT-1 and ACAT-2, with different intracellular localization, membrane topology in mammalian species, and metabolic function for each enzyme [3,4,5]

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