A Commentary on genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms
A Commentary on genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms
复制标题
对全基因组关联研究的评论，该研究旨在识别日本颅内动脉瘤患者中存在的遗传变异
DOI：
10.1038/jhg.2010.93
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发表时间：
2010
期刊：
影响因子：
3.5
通讯作者：
Koizumi A
中科院分区：
文献类型：
--
作者：
新見隆彦;遠藤力;原量宏;辰巳治之;Koizumi A
尽管在过去的几十年里，蛛网膜下腔出血（SAH）在诊断和治疗方面取得了进展，但在大约50%的病例中，SAH是致命的，并在大约30%的幸存者中造成严重的残疾。在日本，SAH的年死亡率估计为每10万人年22.5人。颅内动脉瘤破裂占SAH病例的90%以上。遗传因素、女性性别和生活方式与IA有关。据估计，IA在日本总人口中占比高达2%。由于IA是可预防和可治疗的，因此人们一直期待一种预防策略。预防疾病有两种传统战略：人口战略和高风险战略。对于IA，吸烟和高血压是公认的主要危险因素。这些因素已被视为人口战略的干预工具。从成本效益平衡的角度来看，关注可归因于大量人口的风险以及这些风险因素的禁忌比例可以提供一种实用的方法。但是，预期会有一种更直接的预防战略。根据日本法律，SAH被认为是一种与工作有关的疾病，在工作时间患上SAH的工人经常要求工人赔偿。因此，在工作场所，人口和高风险策略都是可取的。磁共振血管造影（MRA）是否应该用于IA筛查是一个难以解决的问题。MRA是昂贵的，通常不推荐作为筛查一般人群的工具。然而，如果IA的遗传标记是可用的，MRA筛查可用于确定为高风险的人。2008年，Helgadottir等人2报道了单核苷酸多态性（SNP） rs10757278标记的位点是IA的危险因素。Bilguvar等人3报道了一项针对欧洲和日本人群的多阶段全基因组关联研究，并在染色体2q、8q和9p上发现了与IA相关的常见snp。2010年，有三个新的基因座(18q11。2、13个问题。1和10q24。32个基因位点和两个先前确定的位点(8q11。23和9p21。4在本期杂志中，日本团队Akiyama等5报道了日本人群中的5个snp（基因间区rs1930095 （9q31）、TMEM195 （7p21）的rs4628172和rs7781293、ARHGEF11 （1q23）的rs7550260和IQSEC1 （3p25）的rs9864101）。他们推测，由于这三个基因可能在ELN/LIMK通路的肌动蛋白重塑中起作用，这些基因可能是IA易感基因。本研究表明，在日本人群中存在几个值得进一步调查的易感位点。显然，这项研究提供了日本人特有的IA遗传因素的证据。然而，有两个主要问题。人们早就预料到，更多的数据将增加揭示真正遗传因素的信息的统计能力。但事实似乎并非如此。尽管国际联盟已经发表了超过
Despite the diagnostic and therapeutic developments of the past decades, subarachnoid hemorrhage (SAH) is fatal in approximately 50% of cases and causes significant disability in about 30% of the survivors. In Japan, the annual mortality rate from SAH is estimated to be 22.5 per 100000 person-years. Rupture in intracranial aneurysm (IA) accounts for more than 90% of SAH cases. Genetic factors, female gender and lifestyle are associated with IA. IA is estimated to be prevalent in as many as 2% of the general Japanese population. Because IA is preventable and treatable, a strategy for its prevention has long been expected. There are two traditional strategies used for the prevention of diseases: population strategy and high-risk strategy. For IA, it is well established that smoking and hypertension are the major risk factors. These factors have been considered as intervention tools for the population strategy. From the viewpoint of a cost–benefit balance, a focus on risks attributable to large populations and the contraindicated ratios of those risk factors can provide a practical approach. However, a more immediate preventive strategy has been anticipated. Under Japanese law, SAH is considered to be a work-related disease and workers who have SAH attack during working hours have often claimed workers’ compensation. Thus, in the workplace, both population and high-risk strategies are desirable. 1 A difficult question to address is whether magnetic resonance angiography (MRA) should be used for screening for IA. MRA is expensive and is not usually recommended as a tool for screening general populations. However, if a genetic marker for IA is available, MRA screening may be used for persons identified as high risk. In 2008, Helgadottir et al. 2 reported that the locus tagged by the single nucleotide polymorphism (SNP) rs10757278 is a risk factor for IA. Bilguvar et al. 3 reported a multistage genome-wide association study of European and Japanese populations and identified common SNPs associated with IA on chromosomes 2q, 8q and 9p. In 2010, three new loci (18q11. 2, 13q13. 1 and 10q24. 32) were found and two previously identified loci (8q11. 23 and 9p21. 3) were confirmed by an international consortium that included a team from Japan. 4 In this issue of the journal, the Japanese team, Akiyama et al., 5 report five SNPs (rs1930095 of intergenic region (9q31), rs4628172 and rs7781293 of TMEM195 (7p21), rs7550260 of ARHGEF11 (1q23) and rs9864101 of IQSEC1 (3p25)) in a Japanese population. They speculate that, because the three genes may have a role in actin remodeling in the ELN/LIMK pathway, these genes may be IA susceptibility ones. This study indicates the presence of several susceptibility loci in the Japanese population that deserve further investigation. Clearly, this study has provided evidence of genetic factors for IA that are specific to the Japanese. There are, however, two major problems. It has long been anticipated that more data would increase the statistical power of the information revealing genuine genetic factors. This seems not to be so. Although the international consortium has published more than