Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm.
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 FGF1 (chi(2)=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (chi(2)=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.
Yoneyama
Taku
T
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.|Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Kasuya
Hidetoshi
H
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.
Onda
Hideaki
H
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.
Akagawa
Hiroyuki
H
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.|Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Jinnai
Nobuyoshi
N
Theranostics Research Center, Otsuka Pharmaceutical Company, Tokushima, Japan.|Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nakajima
Toshiaki
T
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Hori
Tomokatsu
T
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.
Inoue
Ituro
I
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. ituro@ims.u-tokyo.ac.jp.
D000368:Aged; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D000071840:Fibrillin-2; D000071837:Fibrillins; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*
C000605723:FBN2 protein, human; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D016220:Fibroblast Growth Factor 1; D008249:Protein-Lysine 6-Oxidase