Zhang Jun-hui, Kohara Katsuhiko, Yamamoto Yasumasa, Nakura Jun, Tabara Yasuharu, Fujisawa Mutsuo, Katagi Ryosuke, Miki Tetsuro
Department of Geriatric Medicine, Ehime University School of Medicine, Ehime, Japan.
Cerebrovasc Dis. 2004;17(4):273-9. doi: 10.1159/000077337. Epub 2004 Mar 15.
Lacunar infarction is a unique stroke entity with characteristic symptoms. However, it is often silent clinically. The possible genetic predisposition to symptoms of lacunar infarction was investigated.
One-hundred and fifty-one patients with lacunar stroke were consecutively recruited. Lacunar stroke was diagnosed based on both neurological symptoms and lacunar lesion(s), demonstrated by MRI, that were responsible for the symptoms. One-hundred and fifty control subjects with MRI-proven lacunar lesions without neurological symptoms served as controls. There was no significant difference in age, sex and prevalence of known risk factors between cases and controls. Insertion and deletion polymorphisms of the angiotensin-converting enzyme gene (ACE), M235T substitution of the angiotensinogen gene (AGT), and A1133C substitution of type 1 receptor of the angiotensin II gene were determined.
The frequency of ACE D allele was significantly higher in symptomatic patients compared with asymptomatic subjects (0.44 vs. 0.36, p < 0.05). The genotype distribution of AGT was significantly different between symptomatic and asymptomatic patients (chi(2) = 6.6, p = 0.037). Multiple logistic regression analysis revealed that ACE gene and AGT genotypes were independently associated with the neurological manifestation of lacunar infarction. In subjects with 1 lacuna, the odds ratio of the ACE DD genotype for symptomatic manifestation was 4.98 (95% CI 1.25-19.9). In subjects with 4 or more lacunae, the odds ratio of the ACE II genotype for symptomatic manifestation was 0.24 (95% CI 0.10-0.56). Furthermore, the ACE gene polymorphism was significantly different between symptomatic patients with a single lacuna and asymptomatic subjects with 4 or more multiple lacunar infarctions (chi(2) = 10.6, p = 0.005).
These findings suggest that 2 subtypes of lacunar infarction, single symptomatic lacuna and multiple asymptomatic lacunae, may possess different genetic backgrounds. Subjects with the ACE DD genotype could be more predisposed to be symptomatic in first-ever lacunar stroke, while the ACE II genotype may convey resistance to symptoms even after multiple lacunar strokes. Polymorphism of genes of the renin-angiotensin system could be involved in the manifestation of neurological symptoms of lacunar infarction.
腔隙性脑梗死是一种具有特征性症状的独特卒中类型。然而，其在临床上常无症状。本研究对腔隙性脑梗死症状的可能遗传易感性进行了调查。
连续招募了151例腔隙性卒中患者。腔隙性卒中根据神经症状以及MRI显示的与症状相关的腔隙性病灶进行诊断。150例经MRI证实有腔隙性病灶但无神经症状的对照者作为对照组。病例组和对照组在年龄、性别及已知危险因素患病率方面无显著差异。测定了血管紧张素转换酶基因（ACE）的插入/缺失多态性、血管紧张素原基因（AGT）的M235T替换以及血管紧张素II 1型受体基因的A1133C替换。
有症状患者中ACE D等位基因频率显著高于无症状者（0.44对0.36，p<0.05）。有症状和无症状患者之间AGT的基因型分布存在显著差异（χ²=6.6，p=0.037）。多因素逻辑回归分析显示，ACE基因和AGT基因型与腔隙性脑梗死的神经学表现独立相关。在有1个腔隙的受试者中，ACE DD基因型出现症状表现的比值比为4.98（95%CI 1.25-19.9）。在有4个或更多腔隙的受试者中，ACE II基因型出现症状表现的比值比为0.24（95%CI 0.10-0.56）。此外，单个腔隙的有症状患者与4个或更多多发性腔隙性脑梗死的无症状受试者之间，ACE基因多态性存在显著差异（χ²=10.6，p=0.005）。
这些发现提示，腔隙性脑梗死的两种亚型，即单个有症状腔隙和多个无症状腔隙，可能具有不同的遗传背景。ACE DD基因型受试者在首次腔隙性卒中时更易出现症状，而ACE II基因型即使在多次腔隙性卒中后可能仍对症状具有抵抗力。肾素-血管紧张素系统基因多态性可能与腔隙性脑梗死神经症状的表现有关。
