Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Stroke (Impact Factor: 6.02). 06/2006; 37(5):1189-94. DOI: 10.1161/01.STR.0000217408.91389.4d
Source: PubMed

ABSTRACT 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.
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.
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.
Investigated polymorphisms in this study were not associated with IA.

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    ABSTRACT: Abstract It has been suggested that the elastin gene is a candidate gene for the development of intracranial aneurysms (IAs). We investigated the association of single nucleotide polymorphisms (SNPs) in the elastin gene in sporadic subarachnoid hemorrhage (SAH) and in patients with unruptured aneurysms in China. We genotyped 446 (47.9%) IA patients (308 ruptured and 138 unruptured) and 485 (52.1%) control subjects for seven exonic and intronic SNPs in the elastin gene, and then evaluated their allelic associations with sporadic ruptured and unruptured IAs. We found that IA is associated with two SNPs in the elastin gene: rs2071307 (odds ratio 2.87; 95% confidence interval 2.26-3.64; P<0.001) and rs2856728 (odds ratio 2.12; 95% confidence interval 1.71-2.62; P<0.001). Furthermore, the minor allele of rs2071307 (allele A) was also associated with IA rupture; 31.3% of patients with ruptured IAs were carriers of the minor allele, while only 23.2% of patients with unruptured IAs carried the minor allele (odds ratio 1.51; 95% confidence interval 1.09-2.10; P = 0.013). In conclusion, our study indicates that the elastin gene may be associated with the formation of IAs, and importantly, that it may also be associated with the rupture of IAs.
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