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Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm
Authors:Taku?Yoneyama,Hidetoshi?Kasuya,Hideaki?Onda,Hiroyuki?Akagawa,Nobuyoshi?Jinnai,Toshiaki?Nakajima,Tomokatsu?Hori,Ituro?Inoue  mailto:ituro@ims.u-tokyo.ac.jp"   title="  ituro@ims.u-tokyo.ac.jp"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:(1) Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan;(2) Theranostics Research Center, Otsuka Pharmaceutical Company, Tokushima, Japan;(3) Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Abstract:
We previously performed a genome-wide linkage study of intracranial aneurysm (IA) and found positive evidence of linkage at chromosomes 5q22–31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor 1 (FGF1), fibrillin 2 (FBN2), and lysyl oxidase gene (LOX) lie, and evaluate associations with IA. Genomic DNAs were obtained from 172 IA patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF12=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF12=16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and LOX with IA were detected in the present study.
Keywords:Intracranial aneurysm  Haplotype analysis  Linkage disequilibrium   FGF1    FBN2    LOX
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