Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm
Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm
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DOI：
10.1161/01.str.0000217408.91389.4d
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发表时间：
2006-05-01
期刊：
影响因子：
8.3
通讯作者：
Koizumi, A
中科院分区：
文献类型：
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作者：
Mineharu, Y;Inoue, K;Koizumi, A
背景与目的：已有研究证实颅内动脉瘤（IA）在染色体7q11、17cen、19q13和Xp22上存在连锁。这些区域包含弹性蛋白（ELN）、一氧化氮合成酶2A （NOS2A）、载脂蛋白E （APOE）和血管紧张素- 1转换酶2 (ACE2)，它们被认为是IA的有希望的候选基因。我们的目的是研究这些候选基因中单核苷酸多态性（snp）与IA的关系。方法：为了鉴定NOS2A和ACE2基因多态性，随机选择30例对照，采用直接测序法筛选所有外显子和外显子-内含子边界。tagSNPs程序用于选择单倍型标记的最佳单倍型。对于ELN和APOE， snp选择自先前的报告。然后在362例IA患者和332例居住区匹配对照中对这些选定的snp进行基因分型。利用THESIAS软件通过协变量调整来研究等位基因和单倍型与IA的关联。结果：ELN基因分型8个SNP， NOS2A基因分型8个SNP， APOE基因分型3个SNP， ACE2基因分型1个SNP。4个候选基因的等位基因或单倍型均未显示与IA有显著相关性。结论：本研究中所研究的多态性与IA无关。
Background and Purpose-Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms ( SNPs) with IA in these candidate genes.Methods-To identify polymorphisms in NOS2A and ACE2, all exons and exon-intron boundaries were screened by direct sequencing in 30 randomly selected controls. The program tagSNPs was used to select an optimal set of haplotype-tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These selected SNPs were then genotyped in 362 cases with IA and 332 residential area matched controls. THESIAS software was used to investigate the association of alleles and haplotypes with IA by adjusting with covariates.Results-We genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant association with IA.Conclusions-Investigated polymorphisms in this study were not associated with IA.