Genome-wide scan for Japanese familial intracranial aneurysms - Linkage to several chromosomal regions
Genome-wide scan for Japanese familial intracranial aneurysms - Linkage to several chromosomal regions
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DOI：
10.1161/01.cir.0000143077.23367.18
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发表时间：
2004-12-14
期刊：
影响因子：
37.8
通讯作者：
Koizumi, A
中科院分区：
文献类型：
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作者：
Yamada, S;Utsunomiya, M;Koizumi, A
背景-遗传因素在颅内动脉瘤（IA）的发病机制中起重要作用。先前的研究结果已经提出了几个基因座。方法和结果-我们使用非参数（无模型）方法，使用GENEHUNTER和Merlin软件，对29个IA家族中大于或等于3个个体受IA影响的IA家族进行连锁分析。全基因组连锁分析显示染色体17cen（最大非参数对数比值评分[MNS] = 3.00，标称P = 0.001）、19q13 （MNS = 2.15，标称P = 0.020）和Xp22 （MNS = 2.16，标称P = 0.019）上有3个区域。我们在这些区域检测了4个候选基因：染色体17cen上的微纤维相关蛋白4基因（MFAP4）和诱导型一氧化氮合酶基因（NOS2A）的启动子多态性，染色体19q13上载脂蛋白E基因（APOE）的epsilon基因型，以及染色体Xp22上的血管紧张素I转换酶2基因（ACE2）。通过病例对照研究（100例：来自IA家族的29名先证者和71名与IAs无关的受试者，100名与IAs无关的对照组[未受IAs影响的成员和没有IAs家族史]）评估其多态性与IA的关联。然而，病例对照研究显示，所检测基因的多态性均与IA无关。结论：对29个具有高度家族聚类的日本家庭进行全基因组扫描，发现染色体17cen上有1个提示连锁区域，染色体19q13和Xp22上有2个可能有趣的区域。这些区域与之前在不同人群中的发现一致。
Background - Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci.Methods and Results - From 29 IA families with greater than or equal to3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen ( maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P = 0.001), 19q13 ( MNS = 2.15, nominal P = 0.020), and Xp22 ( MNS = 2.16, nominal P = 0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene ( APOE) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study ( 100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [ unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA.Conclusions - A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.