title: Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions.
abstract: BACKGROUND
  Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci.
  
  
  RESULTS
  From 29 IA families with > or =3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P=0.001), 19q13 (MNS=2.15, nominal P=0.020), and Xp22 (MNS=2.16, nominal P=0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene (APOE) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study (100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA.
  
  
  CONCLUSIONS
  A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamada
authors.forename: Maki
authors.initials: M
authors.lastname: Utsunomiya
authors.forename: Kayoko
authors.initials: K
authors.lastname: Inoue
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nozaki
authors.forename: Sumiko
authors.initials: S
authors.lastname: Inoue
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Takenaka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D041321:Chromosomes, Human, X; D016326:Extracellular Matrix Proteins; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C400752:MFAP4 protein, human; D007703:Peptidyl-Dipeptidase A