血管紧张素转换酶基因多态性与缺血性脑卒中后3个月认知的关系

Relation between ACE gene I/D polymorphism and cognitive impairment at 3 months after ischemic stroke

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与缺血性脑卒中后3个月非痴呆认知功能障碍(CIND)的关系。方法初发缺血性脑卒中患者185例,根据脑卒中后3个月认知功能测定将患者分为CIND组(42例)和对照组(143例)。PCR法测定ACE基因I/D多态性,采用简易智能状态量表和美国精神疾病统计和诊断手册第4版修订本进行认知测定。结果 CIND组与对照组ACE基因I/D多态性的基因型分布与Hardy-Weinberg平衡的理论频数之间差异无统计学意义。单因素分析发现,ACE基因DD基因型人群CIND发病风险是Ⅰ等位基因携带者的2.460倍(95% CI:1.084～5.582,P<0.05)。多因素logistic回归分析发现,在共显性模式中,DD基因型人群CIND发病风险是Ⅱ基因型的3.185倍(95% CI:1.148～8.842,P<0.05);在隐性遗传模式中,DD基因型人群CIND发病风险是Ⅰ等位基因携带者的2.852倍(95% CI:1.058～7.687,P<0.05)。结论ACE DD基因型是缺血性脑卒中后CIND的独立危险因素,携带ACE DD基因型的患者可能更易发生CIND。

Objectives To determine the relation between ACE gene I/D polymorphism and cognitive impairment no dementia（CIND） after ischemic stroke. Methods The perspective nested casecontrol design was applied to the study. The sample consisted of 185 Han people with first-ever ischemic stroke. The ACE gene I/D polymorphism was detected by PCR according to the presence of the intron 16 specific insertion or deletion fragments, 490 kb and 190 kb respeetively（Rigat＇s methods） ,and the possible risk factors involved in CIND were collected in detail. The cognitive function was evaluated at 3 months after stroke according to the Chinese version of MMSE and DSM-Ⅳ-R. CIND was established if a patient with cognitive impairment did not fulfill the DSM-Ⅳ-R criteria of dementia. Results The distribution of genotypes and alleles of ACE gene I/D polymorphism fit Hardy Weinberg equilibrium in both CIND and control groups. Univariate analysis found that the risk for CIND in patients with ACE DD genotype increased by 2. 460 times （DD vs Ⅰ-carrier, P〈 0.05） compared with control subjects. Multivariate logistic regression analysis suggested that the subjects with ACE DD genotype were associated with an increased risk of CIND in recessive model （OR = 2. 852, 95% CI： 1. 058- 7. 687, P 〈 0. 05） or in additive model （OR = 3. 185,95 % CI ： 1. 148- 8. 842, P 〈 0.05）. Conclusions ACE DD genotype was independently associated with CIND after ischemic stroke. The ischemic stroke patients carrying ACE DD genotype might be susceptible to CIND.