Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.
OBJECTIVE
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.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Youhei
Y
Mineharu
Kayoko
K
Inoue
Sumiko
S
Inoue
Shigeki
S
Yamada
Kazuhiko
K
Nozaki
Katsunobu
K
Takenaka
Nobuo
N
Hashimoto
Akio
A
Koizumi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000085962:Angiotensin-Converting Enzyme 2; D001057:Apolipoproteins E / Q000235:genetics*; D004549:Elastin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D001057:Apolipoproteins E; D004549:Elastin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2