Identification of Evidence Suggestive of an Association with Peripheral Arterial Disease at the OSBPL10 Locus by Genome-Wide Investigation in the Japanese Population

DOI 被引用文献3件 参考文献27件
  • Koriyama Hiroshi
    Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
  • Nakagami Hironori
    Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
  • Katsuya Tomohiro
    Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine. Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine.
  • Sugimoto Ken
    Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
  • Yamashita Hidetoshi
    Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
  • Takami Yoichi
    Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
  • Maeda Shiro
    Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN.
  • Kubo Michiaki
    Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN.
  • Takahashi Atsushi
    Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN.
  • Nakamura Yusuke
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo.
  • Ogihara Toshio
    Osaka General Medical Center, Osaka Prefectural Hospital Organization.
  • Rakugi Hiromi
    Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
  • Kaneda Yasufumi
    Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
  • Morishita Ryuichi
    Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine.

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Aim: Peripheral arterial disease (PAD) is a common cause of cardiovascular morbidity and an inde-pendent predictor of cardiovascular mortality. However, little is known about the genetic basis of PAD. To elucidate this, we performed a two-staged genome-wide association study in Japanese indi-viduals.<BR>Methods: We initially tested 222,285 single-nucleotide polymorphisms (SNPs). After the first screen-ing in a panel of 195 PAD cases and 1,358 controls, 2,696 SNPs (1.2%) were further genotyped in the second screening using another panel of 699 PAD cases and 1540 controls. In both screenings, controls were subjects affected with some diseases other than PAD.<BR>Results: When analyzed in the combined panel, the strongest signal of PAD association was observed at rs1902341 in the intron of OSBPL10 (p=4.7E-7 for trend test; OR=1.31, 95% CI 1.18-1.46). Also, PAD was modestly associated at several other loci such as rs2554503 in CSMD1 (p=5.7E-5; OR=1.32, 95% CI 1.15-1.51) or rs235243 in VSP13D (p=0.04; OR=1.18, 95% CI 1.01-1.37).<BR>Conclusion: Our genome-wide exploration identified suggestive evidence of PAD association at the OSBPL10 locus. Because the association has not reached a genome-wide significant level, further replication study is warranted for verification in the Japanese population.

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