Abstract
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 (χ2=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (χ2=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.
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Acknowledgements
This work was supported in part by a Research for the Future Program Grant of the Japan Society for the Promotion of Science (to I. Inoue), Ministry of Public Health and Welfare Research on Human Genome, Tissue Engineering Food Biotechnology (to I. Inoue), a Grant-in-aid for Scientific Research (C) from the Japanese Ministry of Education, Science, Sports and Culture (to H. Kasuya), and Research Found of Mitsukoshi Health and Welfare Foundation 2002 (to H. Onda). We thank Yuka Terada for technical assistance.
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Yoneyama, T., Kasuya, H., Onda, H. et al. Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm. J Hum Genet 48, 309–314 (2003). https://doi.org/10.1007/s10038-003-0030-6
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DOI: https://doi.org/10.1007/s10038-003-0030-6
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