p.E66Q mutation in the GLA gene is associated with a high risk of cerebral small-vessel occlusion in elderly Japanese males
p.E66Q mutation in the GLA gene is associated with a high risk of cerebral small-vessel occlusion in elderly Japanese males
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DOI：
10.1111/ene.12214
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发表时间：
2014-01-01
影响因子：
5.1
通讯作者：
Ikeda, S. -I.
中科院分区：
文献类型：
--
作者：
Nakamura, K.;Sekijima, Y.;Ikeda, S. -I.
背景和目的GLA是Fabry病的致病基因，Fabry病是一种X连锁的溶酶体贮积症，由β-半乳糖苷酶A（-GAL）缺乏引起。脑卒中是法布里病的重要表现，最近的流行病学研究表明，高达4.9%的年轻男性隐源性脑卒中患者存在GLA突变。为了确定GLA突变的重要性，在一般中风人群中，GLA突变的频率在日本男性缺血性中风（IS）患者的各种危险因素和年龄measured.MethodsA共475名男性IS患者（平均年龄69.712.5years），参加了这项研究。获得血液样品以产生用于测量-GAL活性的血点。血液样品与酶活性降低reassayed和整个GLA基因进行了分析，通过直接DNA测序，如果-半乳糖胺A活性始终low.Results-Gal A活性降低10名男子，其中5人（1.1%）有GLA基因突变，p.E66Q。与经典型法布里病患者相比，所有具有p.E66Q突变的IS患者具有大量的残余-Gal A活性。临床上，所有p.E66Q突变患者年龄均> 50岁，并有多处小血管闭塞（腔隙性梗死）。Fisher精确检验统计分析显示GLA p.E66Q等位基因频率在小血管闭塞患者中显著高于日本普通人群[比值比（OR）=3.34，P=0.025）.结论GLA p.E66Q突变是日本老年男性脑小血管闭塞的遗传危险因素。
Background and purposeGLA is the causative gene of Fabry disease, an X-linked lysosomal storage disorder resulting from -galactosidase A (-GAL) deficiency. Stroke is an important manifestation of Fabry disease, and recent epidemiological studies have indicated that up to 4.9% of young male cryptogenic stroke patients have GLA mutations. To determine the importance of GLA mutations in the general stroke population, the frequency of GLA mutations in Japanese male ischaemic stroke (IS) patients with various risk factors and ages was measured.MethodsA total of 475 male IS patients (mean age 69.712.5years), were enrolled in this study. A blood sample was obtained to produce blood spots for measurement of -GAL activity. Blood samples with decreased enzymatic activity were reassayed and the entire GLA gene was analyzed by direct DNA sequencing if -Gal A activity was consistently low.Results-Gal A activity was decreased in 10 men, five of whom (1.1%) had the GLA gene mutation, p.E66Q. All IS patients with p.E66Q mutation had substantial residual -Gal A activity, in contrast to patients with classic-type Fabry disease. Clinically, all patients with p.E66Q mutation were >50years old and had multiple small-vessel occlusions (lacunar infarctions). Statistical analysis using Fisher's exact test showed the allele frequency of GLA p.E66Q in patients with small-vessel occlusion to be significantly higher than that in the general Japanese population [odds ratio (OR)=3.34, P=0.025).ConclusionsGLA p.E66Q mutation is a genetic risk factor for cerebral small-vessel occlusion in elderly Japanese males.