PCSK9基因多态性与急性缺血性脑卒中患者发病风险及阿托伐他汀降脂作用的关系-东南大学学报医学版

PCSK9基因多态性与急性缺血性脑卒中患者发病风险及阿托伐他汀降脂作用的关系

单位：重庆市第五人民医院神经内科, 重庆 400000

关键词：前蛋白转化酶枯草杆菌蛋白酶/溶菌素-9 基因多态性急性缺血性脑卒中阿托伐他汀

分类号：R743.3

出版年·卷·期（页码）：2021·40·第四期（463-468）

摘要：

目的：综合探究前蛋白转化酶枯草杆菌蛋白酶/溶菌素-9（PCSK9）基因多态性与急性缺血性脑卒中（AIS）患者发病风险及阿托伐他汀降脂作用的关系。方法：选取2018年6月至2020年7月间我院神经内科收治的119例AIS患者（设为AIS组），口服阿托伐他汀钙片，每天1次，每次20 mg，共3个月；选取同期120例非心脑血管疾病者作为对照组。比较对照组与AIS组患者PCSK9基因型和等位基因型分布差异，以及不同rs562556基因型的两组（GG组与AG+AA组） AIS患者治疗前后血脂包括甘油三酯（TG）、总胆固醇（TC）、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A1（ApoA1）、载脂蛋白B （ApoB）水平及血清PCSK9水平变化。结果：对照组与AIS组SNP1（rs562556）、SNP2（rs2479408）、SNP3（rs529787）基因型和等位基因分布差异具有统计学意义（P<0.05），且AIS组A和C等位基因型频率较对照组更高。rs562556基因多态性分布与AIS的发生风险密切相关（P<0.05）。治疗后GG组与AG+AA组AIS患者血TC、TG、LDL-C水平均较治疗前降低，血清PCSK9水平均升高（P<0.05）；AG+AA组患者治疗后血TC、TG、LDL-C水平降低程度及PCSK9水平升高程度均大于GG组（P<0.05）。结论：rs562556基因显性模型（GG vs AG+AA）可以增加汉族人群AIS的发病风险，可能是影响阿托伐他汀用于AIS患者降脂治疗作用的重要因素，携带A等位基因者经阿托伐他汀治疗后血清PCSK9水平升高明显，这对于其降脂作用有一定的负面影响。

Objective: To comprehensively explore the relationship between proprotein convertase subtilisin/kexin type 9(PCSK9) gene polymorphism detection and the risk of acute ischemic stroke and the lipid-lowering effect of atorvastatin. Methods: A total of 119 patients with acute ischemic stroke(AIS) admitted to the Department of Neurology of our hospital from June 2018 to July 2020 were selected as research subjects, who received atorvastatin calcium tablets 20 mg once a day for 3 months. One hundred and twenty healthy subjects without heart and brain diseases during the same period were selected as control group. The distribution of PCSK9 genotype and allele was compared between the control group and the AIS group. And the levels of triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), apolipoprotein A1(ApoA1), apolipoprotein B(ApoB) and serum PCSK9 were compared between the two groups before and after treatment in patients with different rs562556 genotypes of AIS. Results: There were statistically significant differences in the genotype and allele distribution of SNP1(rs562556), SNP2(rs2479408) and SNP3(rs529787) between the control group and AIS group(P<0.05), and the allele frequencies of A and C in AIS group were higher than those in the control group(P<0.05). Multivariate Logistic regression analysis showed that rs562556 gene polymorphism distribution was all related to the risk of AIS(P<0.05). After treatment, the levels of TC, TG, LDL-C and ApoB in AIS patients with different rs562556 genotypes in the two groups were decreased compared with those before treatment, while serum PCSK9 levels were increased(P<0.05). In addition, the decrease degree of serum TC, TG, LDL-C levels and the increase degree of serum PCSK9 levels in AG+AA group after treatment were higher than those in GG group(P<0.05). Conclusion: The rs562556 dominant gene model(GG vs Ag+AA) can increase the risk of AIS in Han population, which may be an important factor affecting the lipid-lowering effect of atorvastatin in AIS patients. The serum PCSK9 level of patients carrying A allele is significantly increased after atorvastatin treatment, which has a certain negative effect on the lipid-lowering efficiency.

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