title: Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population.
abstract: Genetic factors are known to have an important role in intracranial aneurysm (IA) pathogenesis. The purpose of this study is to identify single-nucleotide polymorphisms (SNPs) that are associated with IA in Japanese population. A total of 2050 IA patients and 1835 controls recruited in Biobank Japan, The University of Tokyo were used in this study. In all, 45 SNPs in 24 genes encoding proteins, which have been considered to be possible risk factors to IA pathogenesis, were genotyped using multiplex PCR-invader assay. Association analysis was evaluated by logistic regression analysis before and after adjustment of age, smoking and hypertension status. This case-control association study revealed a SNP, rs6460071 located on LIMK1 gene (P = 0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P = 0.00086) and rs243865 (P = 0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P = 0.0026) on tumor necrosis factor-α (TNF-α) gene, are marginally associated with IA in male- and female-specific manner, respectively. In conclusion, a large-scale case-control association study was conducted to verify genetic variations associated with IA in Japanese population. This study gave insights on the importance of stratified analysis between genders, and suggested that the underlying mechanism of IA pathogenesis might differ between females and males.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. yusuke@ims.u-tokyo.ac.jp
authors.forename: Siew-Kee
authors.initials: SK
authors.lastname: Low
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Pei-Chieng
authors.initials: PC
authors.lastname: Cha
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D054461:Lim Kinases / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; C515892:LIMK1 protein, human; D054461:Lim Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2