解密中风与基因的关系
生物探索 · 2014/07/07
中风是老年人中常见的疾病,也是全世界疾病致死病例中的第2大死因。中风受多种风险因素的影响,如高血压、高胆固醇、糖尿病等。2003年冰岛科学家首次发现了与中风相关的基因PDE4D,随后世界各地的科学家们对中风相关的基因展开里广泛的研究。


中风是老年人中常见的疾病,也是全世界疾病致死病例中的第2大死因,并具有在极短时间内从发病到致死的特点。高龄、肥胖、高血压、糖尿病、抽烟、高胆固醇都是引起中风的风险因素。自冰岛科学家在2003年首次发现与中风相关的基因PDE4D以来,随后世界各地的科学家们对中风相关的基因展开了广泛的研究。

病理机制

中风是一组以脑部缺血及出血性损伤症状为主要临床表现的疾病,主要分为出血性脑中风和缺血性脑中风两大类。常见的缺血性中风是由于大脑中血管堵塞,最终形成凝块引起的。中风具有极高的病死率和致残率,以脑梗塞最为常见。高血压是引发中风的主要原因之一。此外,高龄、肥胖、糖尿病、抽烟、高胆固醇都是引起中风的风险因素。

关联基因

2003年,冰岛科学家在《自然遗传学》杂志上报道了第一个与中风相关的基因PDE4D,他们对1800人的研究显示,该基因的微小变化会影响缺血性中风的风险性。动脉粥样硬化是中风的一个关键诱因。科学家们推测,“PDE4D”基因所编码的磷酸二酯酶,有可能是通过影响动脉内平滑肌细胞的增生和扩散,使人患动脉粥样硬化以及随后中风的风险性产生差别。

2009年,美国《新英格兰医学杂志》发表研究报告称,研究人员分析美国和欧洲超过1.9万人基因码后,首次确认普通基因突变与中风发病几率有关。 研究人员发现,常见中风类型缺血性中风与12号染色体上两种相邻基因的变异有关。其中一种基因名为WNK1,另一种为NINJ2。虽然这两种基因突变不大可能是中风的确切基因根源,但可能与这种根源有关。研究人员说,如果体内发生这种基因突变,患缺血性中风几率增加大约30%。

新疆医科大学的研究人员收集2008年1月到2009年12月新疆5所医院294例汉族缺血性卒中患者(病例组)和同期外科系统住院治疗的其他无脑梗死疾病的汉族患者314例(对照组)进行病例对照研究,发现WNK1基因第四内含子rs11611246多态性影响中国人缺血性卒中的发生。 rs11611246位点T等位基因可能是汉族男性发生缺血性卒中的保护因素。

近日,美国《公共科学图书馆-综合》发布的文章报道,基因异常会导致血凝块的形成,从而进一步引发中风的发作。白种人中10个人大约有1个人携带这种名为PIA2的变异基因。伦敦大学国王学院的研究人员发现带着PIA2基因的个体血凝块会阻塞大脑的血液供应,更容易患中风。他们计算出该基因增加一个人患中风的几率为10-15%,拥有该基因两个拷贝的人患中风的风险会增加到70%。PIA2基因可能是对糖蛋白IIIa发挥作用,该蛋白存在于血液中正常的凝血细胞血小板中。血小板在受伤后会引起血块的形成起到止血的作用。科学家认为,带着PIA2基因的个体可能会使得血小板过度活跃。

研究前景

如果你的家族有患中风的历史或者有其它的患中风的风险因素,这并不表明这些风险是不可避免的。相关基因带来的中风风险几率的增加是否具有显著地作用与个体本身的生理条件具有很大的联系。有规律的锻炼,均衡饮食,戒烟都是降低中风风险的重要步骤。

科学家们希望,发展基因检测能够帮助医生预测出更高的患病风险,为医生提供药物治疗和改变他们的生活方式提供依据。今后,科学家们仍然需要对这个测试进行验证,看看它能不能在临床世界发挥作用。中风协会的Shamim Quadir教授表明:“这些最新的研究结果是中风研究中至关重要的一步,我们希望这些研究结果能够使更多处于这种毁灭性疾病中的人被确诊出来”

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  • Genomewide association studies of stroke.

    BACKGROUND: The genes underlying the risk of stroke in the general population remain undetermined. METHODS: We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/-SD] age, 63+/-8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons. RESULTS: Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5x10(-8)). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P=0.04) and 1.42 (95% CI, 1.06 to 1.91; P=0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P=0.03) and 1.19 (95% CI, 1.01 to 1.41; P=0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant. CONCLUSIONS: A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.

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  • The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Stroke: A Systematic Review and Meta-Analysis

    Background The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been reported to be associated with risk of stroke in some studies, although other studies suggest no such association. This meta-analysis and systematic review was conducted to investigate the hypothesis that carriage of the PlA2 allele is a risk factor for stroke. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Findings A total of 35 articles were eligible for inclusion, of which 25 studies were suitable for statistical analysis. For carriage of the PlA2 allele, OR 1.12 (n = 11,873; 95% CI = 1.03–1.22; p = 0.011) was observed for the incidence of stroke in adults, with subgroup analyses identifying the association driven by stroke of an ischaemic (n = 10,494; OR = 1.15, 95% CI = 1.05–1.27; p = 0.003) but not haemorrhagic aetiology (n = 2,470; OR = 0.90, 95% CI = 0.71–1.14; p = 0.398). This association with ischaemic stroke was strongest in individuals homozygous for the PlA2 allele compared to those homozygous for wild-type PlA1 (n = 5,906; OR = 1.74, 95% CI = 1.34–2.26; p<0.001). Subgroup analysis of ischaemic stroke subtypes revealed an increased association with stroke of cardioembolic (n = 1,271; OR 1.56, 95% CI 1.14–2.12; p = 0.005) and large vessel (n = 1,394; OR = 1.76, 95% CI 1.34–2.31; p<0.001) aetiology, but not those of small vessel origin (n = 1,356; OR = 0.99, 95% CI 0.74–1.33; p = 0.950). Egger's regression test suggested a low probability of publication bias for all analyses (p>0.05). Conclusions The totality of published data supports the hypothesis that carriage of the PlA2 polymorphism of GPIIIa is a risk factor for ischaemic strokes, and specifically those of cardioembolic and large vessel origin.

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