ApoE基因型与颈动脉粥样硬化及脑梗死的相关性研究

黄柳; 戴昕好; 田雪; 姚菁青; 戴悦; 李云涛

doi:10.16766/j.cnki.issn.1674-4152.002042

ApoE基因型与颈动脉粥样硬化及脑梗死的相关性研究

doi: 10.16766/j.cnki.issn.1674-4152.002042

黄柳¹,
戴昕好²,
田雪¹,
姚菁青¹,
戴悦¹,
李云涛^2, ,

1.
南京医科大学第二临床医学院，江苏南京 210011
2.
南京医科大学第二附属医院全科医学科，江苏南京 210011

基金项目:

江苏省卫健委十三五“科教强卫工程”青年医学重点人才资助项目 QNRC2016677

南京医科大学研究生教育教学改革课题 SPOCYB201913

详细信息

通讯作者:
李云涛, E-mail: liyuntao78@njmu.edu.com

中图分类号: R743 R543.5
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出版历程
- 收稿日期: 2020-08-17
- 网络出版日期: 2022-02-16

Correlation between ApoE genotype and carotid atherosclerosis and cerebral infarction

1.
Department of General Medicine, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China

摘要

摘要: 目的探讨人类载脂蛋白E(apolipoprotein e，ApoE)基因型与颈动脉粥样斑块稳定性、位置分布及脑梗死的相关性。方法随机选取南京医科大学第二附属医院2019年1月1日—12月31日期间275名行颈动脉B超、ApoE基因检测、血脂检测及头颅核磁共振的住院患者进行分析，根据颈动脉B超检查分为对照组88例、稳定斑块组71例和不稳定斑块组116例，将颈动脉粥样硬化(carotid atherosclerosis, CAS)患者分为脑梗死组和无脑梗死组进行研究分析。结果 (1) 人群中ε2基因频率为10.7%，ε3为78.2%，ε4为11.1%。(2)不稳定斑块组与对照组相比，基因型分布差异有统计学意义(P=0.008)，与ε3/ε3基因型相比，ε3/ε4(OR=3.115，95% CI：1.314~7.388)更易导致不稳定斑块。(3)ApoE基因型与颈动脉斑块位置无明显关系(χ²=3.190，P=0.527)。(4)在已发生CAS患者中，与非ε2携带者比较，ε2携带者(χ²=4.285，P=0.038)不易发生脑梗死。(5)在CAS患者中，调整年龄、性别、高血压、糖尿病因素后，ε2等位基因是脑梗死的保护因素(P=0.023, OR=0.352，95% CI：0.144~0.865)。结论基因型ε3/ε4可能是导致患者颈动脉不稳定性粥样斑块形成的危险因素, ApoE基因型与颈动脉粥样硬化性斑块的分布位置无关。ε2等位基因是已发生CAS的患者发生脑梗死的保护因素。
- 载脂蛋白E /
- 基因多态性 /
- 动脉粥样硬化 /
- 脑梗死
Abstract: Objective To study the correlation between apolipoprotein E (ApoE) genotype and the stability and location of carotid atherosclerotic plaque and cerebral infarction. Methods Total 275 patients from the Second Affiliated Hospital of Nanjing Medical University from January 1, 2019 to December 31, 2019 were divided into three groups according to the results of carotid ultrasound examinations: control group (88 cases), stable plaque group (71 cases) and unstable plaque group (116 cases). The ApoE genotype and blood lipid were determined. Patients with carotid atherosclerosis were inspected using head MRI. CAS patients were divided into the cerebral infarction group and no cerebral infarction group according to the MRI results. Results (1) The frequencies of ε2, ε3 and ε4 genes in the population were 10.7%, 78.2% and 11.1%, respectively, which conform to the law of genetic balance. (2) Significant differences were observed in the genotype distribution (P=0.008) between the unstable plaque group and the control group, and ε3/ε4 genotype (OR=3.115, 95% CI: 1.314-7.388) was more likely to lead to unstable plaques than the ε3/ε3 genotype. (3) The ApoE genotype had no significant relationship with the location of carotid plaque (χ²=3.190, P=0.527). (4) ε2 carriers (χ²=4.285, P=0.038) were less likely to have cerebral infarction than non- ε2 carriers with carotid atherosclerosis. (5) The ε2 allele was a protective factor for cerebral infarction in CAS patients after adjusting for age, sex, hypertension and diabetes (P=0.023, OR=0.352, 95% CI: 0.144-0.865). Conclusion The ε3/ε4 genotype may be a risk factor for the formation of unstable carotid atherosclerotic plaque. The ApoE genotype is not related to the location of carotid atherosclerotic plaque. The ε2 allele is a protective factor for cerebral infarction in CAS patients.
- Apolipoprotein E /
- Gene polymorphism /
- Atherosclerosis /
- Cerebral infarction

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表 1 非CAS与CAS患者一般情况比较

组别	例数	年龄(x±s，岁)	男性[例(%)]	高血压[例(%)]	糖尿病[例(%)]	TG(x±s，mmol/L)	TC(x±s，mmol/L)	LDL-C(x±s，mmol/L)	HDL-C(x±s，mmol/L)
对照组	88	57.6±11.4	37(42.0)	64(72.7)	10(11.4)	1.59±0.98	4.11±1.01	2.63±0.89	1.31±0.48
稳定斑块组	71	68.5±11.1^a	34(47.9)	64(90.1)^a	19(26.7)^a	1.78±1.13	4.13±1.09	2.64±1.13	1.24±0.35
不稳定斑块组	116	66.5±10.4^a	66(56.8)	100(86.2)^a	36(31.0)^a	1.79±1.21	4.22±1.05	2.75±1.06	1.16±0.32^a
统计量		24.313^b	4.557^c	9.949^c	11.245^c	0.929^b	0.334^b	0.435^b	3.685^b
P值		<0.001	0.102	0.007	0.004	0.396	0.716	0.648	0.026
注：与对照组比较，^aP＜0.05；^b为F值，^c为χ²值。

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表 2 不同颈动脉粥样硬化斑块患者ApoE基因型分布情况 (例)

组别	例数	ApoE基因型						基因频率(%)
组别	例数	ε2/ε2	ε2/ε3	ε2/ε4	ε3/ε3	ε3/ε4	ε4/ε4	ε2	ε3	ε4
对照组	88	1	14	5	60	8	0	21(11.9)	142(80.7)	13(7.4)
稳定斑块组	71	0	13	3	47	7	1	16(11.3)	114(80.3)	12(8.4)
不稳定斑块组	116	2	17	1	65	27	4	22(9.5)	174(75.0)	36(15.5)
注：ApoE基因型分布比较，采取Fisher精确检验，P=0.031；基因频率分布比较, χ²=8.301, P=0.081。

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表 3 不同颈动脉斑块位置CAS患者ApoE基因型表现

斑块位置数量	ApoE基因表现型
斑块位置数量	E2	E3	E4
1处	16	63	19
2处	10	43	14
3处及以上	6	10	6
注：ApoE表现型E2为(ε2/ε2，ε2/ε3)，E3为(ε3/ε3，ε2/ε4)，E4为(ε3/ε4，ε4/ε4)，χ²=3.190，P=0.527。

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表 4 不同ApoE基因型CAS患者血脂水平比较(x ±s，mmol/L)

ApoE基因型	例数	TG	TC	LDL	HDL
ε2/ε2	3	2.64±1.41^a	4.75±1.28	2.67±0.74	1.19±0.20
ε2/ε3	44	2.20±1.57^a	4.15±1.08	2.44±0.98	1.21±0.39
ε2/ε4	9	1.79±0.81	3.56±0.54	1.93±0.73	1.14±0.53
ε3/ε3	172	1.56±0.88	4.12±1.01	2.72±0.99	1.23±0.38
ε3/ε4	42	1.84±1.36	4.41±1.19	2.87±1.25	1.28±0.40
ε4/ε4	5	1.27±0.47	4.11±0.48	2.89±0.69	1.23±0.38
F值		3.135	1.310	1.829	0.222
P值		0.009	0.260	0.107	0.953
注：与其他基因型比较，^aP＜0.05。

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表 5 有无脑梗死颈动脉粥样硬化患者ApoE基因型携带情况(例)

组别	例数	ε2基因		ε3基因		ε4基因
组别	例数	携带	非携带	携带	非携带	携带	非携带
脑梗死组	71	8	63	69	2	16	55
无脑梗死组	115	27	88	106	9	27	88
χ²值		4.285				0.022
P值		0.038		0.210^a		0.882
注：^a为采用Fisher精确检验。

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表 6 颈动脉硬化患者中ε2与脑梗死的关系

变量	B	SE	Wald χ²	P值	OR值	95% CI
年龄	0.059	0.017	11.96	0.001	1.061	1.026~1.097
性别	0.658	0.345	3.64	0.056	1.932	0.982~3.800
高血压	0.916	0.558	2.70	0.101	2.499	0.838~7.453
糖尿病	0.876	0.353	6.16	0.013	2.401	1.202~4.795
携带ε2基因	-1.043	0.458	5.19	0.023	0.352	0.144~0.865
注：调整年龄、性别、高血压、糖尿病因素。脑梗死，有=1，无=0；性别，男=1，女=0；高血压，有=1，无=0；糖尿病，有=1，无=0；ε2基因，携带=1，非携带=0；连续变量以实际值赋值。

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