Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population

Siew Kee Low, Hitoshi Zembutsu, Atsushi Takahashi, Naoyuki Kamatani, Pei Chieng Cha, Naoya Hosono, Michiaki Kubo, Koichi Matsuda, Yusuke Nakamura

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (P0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P0.00086) and rs243865 (P0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P0.0026) 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.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalJournal of Human Genetics
Volume56
Issue number3
DOIs
Publication statusPublished - 01-03-2011

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Intracranial Aneurysm
Metalloproteases
Tumor Necrosis Factor-alpha
Single Nucleotide Polymorphism
Population
Case-Control Studies
Genes
Social Adjustment
Tokyo
Multiplex Polymerase Chain Reaction
Japan
Logistic Models
Smoking
Regression Analysis
Hypertension

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Low, S. K., Zembutsu, H., Takahashi, A., Kamatani, N., Cha, P. C., Hosono, N., ... Nakamura, Y. (2011). Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population. Journal of Human Genetics, 56(3), 211-216. https://doi.org/10.1038/jhg.2010.169
Low, Siew Kee ; Zembutsu, Hitoshi ; Takahashi, Atsushi ; Kamatani, Naoyuki ; Cha, Pei Chieng ; Hosono, Naoya ; Kubo, Michiaki ; Matsuda, Koichi ; Nakamura, Yusuke. / Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population. In: Journal of Human Genetics. 2011 ; Vol. 56, No. 3. pp. 211-216.
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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 (P0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P0.00086) and rs243865 (P0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P0.0026) 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.",
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Low, SK, Zembutsu, H, Takahashi, A, Kamatani, N, Cha, PC, Hosono, N, Kubo, M, Matsuda, K & Nakamura, Y 2011, 'Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population', Journal of Human Genetics, vol. 56, no. 3, pp. 211-216. https://doi.org/10.1038/jhg.2010.169

Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population. / Low, Siew Kee; Zembutsu, Hitoshi; Takahashi, Atsushi; Kamatani, Naoyuki; Cha, Pei Chieng; Hosono, Naoya; Kubo, Michiaki; Matsuda, Koichi; Nakamura, Yusuke.

In: Journal of Human Genetics, Vol. 56, No. 3, 01.03.2011, p. 211-216.

Research output: Contribution to journalArticle

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T1 - Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population

AU - Low, Siew Kee

AU - Zembutsu, Hitoshi

AU - Takahashi, Atsushi

AU - Kamatani, Naoyuki

AU - Cha, Pei Chieng

AU - Hosono, Naoya

AU - Kubo, Michiaki

AU - Matsuda, Koichi

AU - Nakamura, Yusuke

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N2 - 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 (P0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P0.00086) and rs243865 (P0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P0.0026) 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.

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