Association between ACAT-1 rs1044925 SNP and Acute Coronary Syndrome and Change of Serum Lipid Level in Response to Atorvastatin Treatment

doi:10.12114/j.issn.1007-9572.2022.0069

Abstract

Abstract:

Background

Previous studies have shown that the rs1044925 single nucleotide polymorphism (SNP) of ACAT-1 gene is associated with the risk of coronary heart disease and ischemic stroke, and both are correlated to the level of blood lipid.

Objective

To observe the relationship between rs1044925 SNP of ACAT-1 gene and acute coronary syndrome (ACS) , and the relationship between rs1044925 SNP and the change of serum lipids level in response to atorvastatin treatment in patients with ACS.

Methods

111 patients diagnosed with ACS and treated with percutaneous coronary intervention (PCI) in the Department of Geriatric Cardiovascular, People's Hospital of Guangxi Zhuang Autonomous from January 2016 to January 2018 were selected in ACS group (67 males and 44 females) . All patients were treated with atorvastatin 20 mg per night, Clopidogrel 75 mg, once a day (or tegranolol 90 mg, twice a day) , and Aspirin 100 mg, once a day. Atorvastatin 20 mg/night was routinely used after PCI. The control group consisted of 338 healthy people in the same time period (170 males and 168 females) . ACAT-1 rs1044925 SNP was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) . The baseline blood lipid levels of ACS group and control group were detected. The blood lipid parameters of the ACS group were measured after treatment of atorvastatin for one year averagely.

Results

There was no statistical difference in serum TC between the ACS group and the control group (P>0.05) , but there were statistical differences in the levels of TG, HDL-C, LDL-C, ApoAI, and ApoB (P<0.05) between the two gruops. There was no statistical difference in the distribution of ACAT-1 rs1044925 SNP genotype and allele frequency between the ACS group and the control group (P>0.05) . There was no statistical difference in the levels of TC, TG, HDL-C, LDL-C, ApoAI and ApoB among each genotype group of ACAT-1 rs1044925 SNP in the control group (P>0.05) . After atorstatin treatment, the serum TC, LDL-C, ApoAI, ApoB and lipoprotein (Lp) (α) levels in ACS patients were statistically different from baseline levels (P<0.05) . There was no statistical difference in the levels of TC, TG, HDL-C, LDL-C, ApoAI, and ApoB at baseline among the genotypes from starting point and one year later in the ACS group (P>0.05) . There was no statistical difference in the baseline of Lp (α) level among genotypes (P>0.05) in ACS patients, but after 1 year of treatment, the Lp (α) level of each genotype was statistically different (P<0.05) . Comparing baseline levels with the levels of TC, LDL-C, ApoAI, ApoB, Lp (α) after treatment in patients with AA genotype and comparing baseline levels with the levels of TC, LDL-C, ApoB levels in patients with AC/CC genotype after treatment, the differences were statistically significant (P<0.05) . Comparing the decrease in the levels of TC, LDL-C, ApoB with the increase of level in ApoAI after atorvastatin treatment between different genotypes, there was no statistical difference (P>0.05) . There was statistical difference among the decrease in the levels of Lp (α) after atorvastatin treatment among different genotypes (P<0.05) .

Conclusion

This study demonstrates that the ACAT-1 rs1044925 SNP is not significantly associated with ACS. However, ACS patients with rs1044925 SNP AA genotype have better decreasing effect in Lp (α) level than patients with AC/CC genotype after atorvastatin treatment.

Key words: Acute coronary syndrome, Cholesterol acyltransferase 1, ACAT-1 rs1044925, Single nucleotide polymorphism, Atorvastatin, Blood lipid

摘要：

背景

既往研究显示ACAT-1 rs1044925单核苷酸多态性（SNP）与冠心病及缺血性脑卒中的发病风险相关，并且与血脂水平有关。

目的

本研究旨在探讨ACAT-1 rs1044925 SNP与急性冠脉综合征（ACS）的关系，以及rs1044925 SNP与ACS患者阿托伐他汀治疗后调脂效果的关系。

方法

选择2016年1月—2018年1月在广西壮族自治区人民医院老年心血管内科确诊为ACS并接受经皮冠状动脉介入治疗（PCI）的患者111例作为ACS组（男67例，女44例）；患者均接受阿托伐他汀治疗，20 mg/晚；同时服用氯吡格雷75 mg，1次/d（或替格瑞洛90 mg，2次/d），阿司匹林100 mg，1次/d；并在经PCI后常规使用阿托伐他汀，20 mg/晚。对照组为同期体检健康人群，共338例（男170例，女168例）。通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）对ACAT-1 rs1044925 SNP进行基因分型，检测ACS组和对照组的基线血脂水平，随访检测ACS组患者阿托伐他汀治疗1年后血脂参数。

结果

ACS组和对照组受检者的血清总胆固醇（TC）间差异无统计学意义（P>0.05），而三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白AI（ApoAI）、载脂蛋白B（ApoB）水平间差异均有统计学意义（P<0.05）。ACS组和对照组的ACAT-1 rs1044925 SNP基因型及等位基因频率的分布间差异均无统计学意义（P>0.05）。对照组ACAT-1 rs1044925 SNP的各基因型间TC、TG、HDL-C、LDL-C、ApoAI及ApoB水平比较，差异无统计学意义（P>0.05）。阿托伐他汀治疗后，ACS患者血清TC、LDL-C、ApoAI、ApoB及脂蛋白α〔Lp（α）〕水平与基线水平比较，差异均有统计学意义（P<0.05）。ACS组各基因型患者间的基线及1年后的TC、TG、HDL-C、LDL-C、ApoAI、ApoB水平比较，差异均无统计学意义（P>0.05）；ACS组不同基因型患者间的基线Lp（α）水平差异无统计学意义（P>0.05），而治疗1年后，各基因型患者间的Lp（α）水平比较，差异有统计学意义（P<0.05）。AA基因型患者治疗后的TC、LDL-C、ApoAI、ApoB、Lp（α）水平与基线水平比较，以及AC/CC基因型患者治疗后的TC、LDL-C、ApoB水平与基线水平比较，差异均有统计学意义（P<0.05），不同基因型患者间阿托伐他汀治疗后TC、LDL-C、ApoB水平降低程度和ApoAI升高程度比较，差异无统计学意义（P>0.05），不同基因型患者间阿托伐他汀治疗后Lp（α）水平降低程度比较，差异有统计学意义（P<0.05）。

结论

ACAT-1 rs1044925 SNP与ACS没有明显关联，ACS患者接受阿托伐他汀治疗后，rs1044925 SNP AA基因型患者较AC/CC基因型患者Lp（α）降低更明显。

关键词: 急性冠状动脉综合征, 胆固醇酰基转移酶1, ACAT-1 rs1044925, 单核苷酸多态性, 阿托伐他汀, 血脂

WANG Zhou,DENG Jinlong,WU Dongfeng. Association between ACAT-1 rs1044925 SNP and Acute Coronary Syndrome and Change of Serum Lipid Level in Response to Atorvastatin Treatment[J]. Chinese General Practice, 2023, 26(21): 2620-2625. DOI: 10.12114/j.issn.1007-9572.2022.0069.
王舟,邓金龙,吴东峰. ACAT-1 rs1044925单核苷酸多态性与急性冠脉综合征及阿托伐他汀治疗后血脂反应的关系研究[J]. 中国全科医学, 2023, 26(21): 2620-2625. DOI: 10.12114/j.issn.1007-9572.2022.0069.

Figures/Tables 6

References 23

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组别	例数	性别（男/女）	年龄（±s，岁）	BMI （±s，kg/m²）	糖尿病〔n（%）〕	高血压〔n（%）〕
对照组	338	170/168	64.1±7.7	23.2±3.0	27（8.0）	92（27.2）
ACS组	111	67/44	64.3±10.1	23.8±3.2	11（9.9）	39（35.1）
t（χ²）值		3.396^a	-0.166	1.580	0.398^a	2.534^a
P值		0.065	0.869	0.115	0.528	0.111

组别	例数	性别（男/女）	年龄（±s，岁）	BMI （±s，kg/m²）	糖尿病〔n（%）〕	高血压〔n（%）〕
对照组	338	170/168	64.1±7.7	23.2±3.0	27（8.0）	92（27.2）
ACS组	111	67/44	64.3±10.1	23.8±3.2	11（9.9）	39（35.1）
t（χ²）值		3.396^a	-0.166	1.580	0.398^a	2.534^a
P值		0.065	0.869	0.115	0.528	0.111

组别	例数	TC（mmol/L）	TG（mmol/L）	HDL-C（mmol/L）	LDL-C（mmol/L）	ApoAI（g/L）	ApoB（g/L）
对照组	338	4.93±0.96	1.26±1.38	1.86±0.47	2.79±0.77	1.39±0.26	0.88±0.20
ACS组	111	4.82±1.06	1.67±1.06	1.10±0.28	3.01±0.81	1.14±0.25	0.99±0.23
t值		1.003	-2.859	16.046	-2.598	9.015	-4.668
P值		0.316	0.004	<0.001	0.010	<0.001	<0.001

组别	例数	TC（mmol/L）	TG（mmol/L）	HDL-C（mmol/L）	LDL-C（mmol/L）	ApoAI（g/L）	ApoB（g/L）
对照组	338	4.93±0.96	1.26±1.38	1.86±0.47	2.79±0.77	1.39±0.26	0.88±0.20
ACS组	111	4.82±1.06	1.67±1.06	1.10±0.28	3.01±0.81	1.14±0.25	0.99±0.23
t值		1.003	-2.859	16.046	-2.598	9.015	-4.668
P值		0.316	0.004	<0.001	0.010	<0.001	<0.001

组别	例数	rs1044925			等位基因
组别	例数	AA	AC	CC	A	C
对照组	338	239（70.7）	95（28.1）	4（1.2）	32（14.4）	103（15.2）
ACS组	111	81（73.0）	28（25.2）	2（1.8）	190（85.6）	573（84.8）
χ²值		0.552			0.088
P值		0.759			0.766