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.
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Acknowledgements
We express our heartfelt gratitude to all the patients who participate in this study. Our thankfulness also goes to the member of The Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for making this study possible. We would like to express our gratefulness to the staff from Biobank Japan for their outstanding assistance. This work was conducted as a part of Biobank Japan Project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology from the Japanese Government. In addition, this work is performed in collaboration with Center of Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN).
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Low, SK., Zembutsu, H., Takahashi, A. et al. Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population. J Hum Genet 56, 211–216 (2011). https://doi.org/10.1038/jhg.2010.169
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DOI: https://doi.org/10.1038/jhg.2010.169
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