ADAMTS基因多态性与脑梗死体检患者颈动脉粥样硬化性斑块易损性及阿托伐他汀降脂疗效的相关性研究

Association of the gene polymorphism of ADAMTS with the vulnerability of carotid atherosclerotic plaque and the lipid-lowering efficacy of atorvastatin in patients with cerebral infarction

摘要:

目的 探讨Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶（a disintegrin and metalloproteinase with thrombospondin type 1 motifs，ADAMTS）基因多态性与脑梗死体检患者颈动脉粥样硬化性斑块易损性及阿托伐他汀降脂疗效的相关性。方法 收集2016年1月至2019年1月河北医科大学第一医院收治的684例脑梗死体检患者的临床资料，根据颈动脉超声检查结果分为稳定斑块组（338例）和易损斑块组（346例）。比较2组患者的一般资料、生化检测指标、ADAMTS rs402007（G/C）位点基因型及等位基因频率。采用Logistic回归分析探讨颈动脉粥样硬化性斑块易损性的危险因素和ADAMTS基因多态性与危险因素在颈动脉粥样硬化性斑块易损性中的交互作用。比较不同基因型患者阿托伐他汀降脂疗效，分析不同基因型与阿托伐他汀疗效的相关性。结果 稳定斑块组和易损斑块组糖尿病比例及低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）、总胆固醇（total cholesterol，TC）、同型半胱氨酸（homocysteine，HCY）、纤维蛋白原（fibrinogen，FIB）水平的比较差异有统计学意义（P<0.05）。2组患者间GG基因型与GC+CC基因型分布的比较差异有统计学意义（P<0.05）。糖尿病、LDL-C、HCY、FIB是影响颈动脉粥样硬化性斑块易损性的危险因素（P<0.05）。LDL-C与ADAMTS基因rs402007位点存在交互作用（P<0.05）。GG、GC、CC基因型组阿托伐他汀降脂治疗有效率分别为144例（82.29%）、209例（84.27%）、233例（89.27%）。各基因型患者阿托伐他汀治疗前后血脂水平比较差异有统计学意义（P<0.05）。稳定斑块组和易损斑块组治疗前、治疗后LDL-C水平，以及治疗后高密度脂蛋白胆固醇、甘油三酯、TC水平比较差异有统计学意义（P<0.05）。以GG基因型为参考，GC基因型与阿托伐他汀治疗的疗效无相关性（P>0.05），CC基因型与疗效有相关性（P<0.05）。结论 ADAMTS基因多态性与颈动脉粥样硬化性斑块易损性存在相关性，与阿托伐他汀的降脂疗效存在相关。

Abstract:

Objective To investigate the association of the gene polymorphism of a disintegrin and metalloproteinase with thrombospondin type 1 motifs （ADAMTS） with the vulnerability of carotid atherosclerotic plaque and the lipid-lowering efficacy of atorvastatin in patients with cerebral infarction.Methods Clinical data were collected from 684 patients with cerebral infarction who were admitted to The First Hospital of Hebei Medical University from January 2016 to January 2019， and according to the results of carotid artery sonography， they were divided into stable plaque group with 338 patients and vulnerable plaque group with 346 patients. The two groups were compared in terms of general information， biochemical parameters， and genotype and allele frequencies at rs402007 （G/C） locus. A logistic regression analysis was used to investigate the risk factors for carotid atherosclerotic plaque vulnerability and the interaction between rs402007 gene polymorphisms and risk factors in carotid atherosclerotic plaque vulnerability. The lipid-lowering efficacy of atorvastatin was compared between the patients with different genotypes， and the association between genotype and the efficacy of atorvastatin was analyzed.Results There were significant differences between the two groups in diabetes， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， homocysteine （HCY）， and fibrinogen （FIB） （P<0.05）. There were also significant differences in GG genotype and GC+CC genotype between the two groups （P<0.05）. Diabetes， LDL-C， HCY， and FIB were risk factors for the vulnerability of carotid atherosclerotic plaque （P<0.05）， and there was interaction between LDL-C and rs402007 gene （P<0.05）. The response rates of the GG， GC， and CC genotype were 82.29% （144 cases）， 84.27% （209 cases）， and 89.27% （233 cases）， respectively. There were significant changes in blood lipid levels in the patients with different genotypes after treatment （P<0.05）. There were significant differences between the two groups in LDL-C before and after treatment and high-density lipoprotein cholesterol， triglyceride， and total cholesterol after treatment （P<0.05）. With GG genotype as a reference， there was no association between GC genotype and efficacy （P>0.05）， and there was an association between CC genotype and efficacy （P<0.05）.Conclusions ADAMTS gene polymorphism is associated with the vulnerability of carotid atherosclerotic plaque and the lipid-lowering efficacy of atorvastatin.