半胱氨酸蛋白酶抑制剂C基因G73A位点和载脂蛋白E基因多态性与血管性认知障碍的临床研究

目的探讨半胱氨酸蛋白酶抑制剂C基因(CST3)G73A位点和载脂蛋白E(APOE)基因多态性与血管性认知功能障碍(VCI)的关系。 方法采用病例-对照研究，收集2015年1至6月青岛大学附属医院神经内科门诊、住院患者与同期门诊健康体检者，其中血管性认知障碍(VCI)患者155例，无认知损害的脑梗死(CI)患者210例，同期健康体检者(ND)250例。应用限制性片段长度多态性聚合酶链反应(PCR/RFLP)技术检测CST3 G73A位点和APOE基因的多态性。应用卡方检验进行基因型及等位基因分析，经多元Logstic回归纠正影响因素后分析这两种基因多态性对VCI的影响。 结果CST3 G73A位点基因型频率(χ²＝3.40，P＝0.18)及等位基因频率(χ²＝3.95，P＝0.14)均差异无统计学意义；APOE ε4/4基因携带型与非携带型比较，发生VCI的风险是CI组4.98倍(P<0.01，95%CI：1.94～12.80)，是ND组的5.68倍(P<0.01，95%CI：2.22～14.60)。将CST3 G73A位点与APOE基因经多元Logstic回归纠正相关危险因素后，结果表明，G73A位点为AA突变型时，APOE ε4/4基因携带型发生VCI的风险是CI组的7.19倍(纠正OR：6.30，95%CI：1.34～29.60，P＝0.013)，是ND组的8.22倍(纠正OR：7.26，95%CI：1.55～34.10，P＝0.008)。 结论CST3 G73A位点AA基因突变型可能增加APOE ε4/4基因携带型发生VCI的发病风险。

The relationship between cystatin C gene G73A locus and appolipoprotein E gene polymorphisms and vascular cognitive impairment

ObjectiveTo investigate the relationship of cystatin C gene (CST3) G73A locus and apolipoprotein E (APOE) gene polymorphisms with vascular cognitive impairment(VCI). MethodsA case-control study was conducted to collect outpatients and inpatients of Neurology department, and healthy subjects in the same period in Affiliated Hospital of Qingdao University from January to June 2015, including 155 patients with VCI, 210 patients with cerebral infarction (CI) without cognitive impairment and 250 healthy subjects as control group (ND). Polymerase chain reaction/restrictive fragment length polymorphism (PCR/RFLP) was used to detect the polymorphism of CST3 G73A and APOE genes. The chi-square test was used to perform genotype and allele analysis. The effects of these two gene polymorphisms on VCI were analyzed by multivariate Logstic regression which to correct the influencing factors. ResultsNo statistical differences were demonstrated in CST3 G73A locus genotype frequencies (χ²=3.95, P=0.14) and allele frequencies (χ²=3.95, P=0.14). Compared with non-carrying type, the risk of developing VCI in APOE ε4/4 gene-carrying type is 4.98 times higher than that of CI group (P<0.01, 95%CI: 1.94-12.80), while 5.68 times higher than that of ND group (P<0.01, 95%CI: 2.22-14.60). After correcting the risk factors of the CST3 gene G73A locus and the APOE gene by multiple Logistic regression, the results showed that when the G73A locus was AA mutant, the risk of VCI in the APOE ε4/4 gene-carrying type was 7.19 times higher than that of the CI group (corrected OR: 6.30, 95%CI: 1.34-29.60, P=0.013), while 8.22 times higher than that of the ND group (OR: 7.26, 95%CI: 1.55-34.10, P=0.008). ConclusionThe AA gene mutation of G73A locus in CST3 may increase the risk of VCI in APOE ε4/4 gene-carrying type.