Nakano Masakazu, Ikeda Yoko, Tokuda Yuichi, Fuwa Masahiro, Ueno Morio, Imai Kojiro, Sato Ryuichi, Omi Natsue, Adachi Hiroko, Kageyama Masaaki, Mori Kazuhiko, Kinoshita Shigeru, Tashiro Kei
1] Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan [2].
1] Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan [2].
Sci Rep. 2014 Jun 18;4:5340. doi: 10.1038/srep05340.
The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and Caucasian populations. Therefore, we newly performed a genome-wide association study using 201 XFS/XFG and 697 controls in Japanese, and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus. These SNPs were confirmed by an independent population consisted of 121 XFS/XFG and 263 controls in Japanese. Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population. Although there still should be other gene(s) in the other region(s) contributing to the disease process, these results suggested that the combination of newly discovered variants in these genes might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.
赖氨酰氧化酶样1基因（LOXL1）的常见变异与通过剥脱综合征（XFS）发展而来的剥脱性青光眼（XFG）患者相关。然而，已发现LOXL1中一个变异的风险等位基因在亚洲人和白种人群体之间是相反的。因此，我们新开展了一项全基因组关联研究，使用了201例日本XFS/XFG患者和697例对照，在15q24.1位点鉴定出34个全基因组显著的单核苷酸多态性（SNP），这些SNP不仅分布在LOXL1，还分布在TBC1D21和PML基因中。这些SNP在一个由121例日本XFS/XFG患者和263例对照组成的独立群体中得到了验证。此外，进一步分析揭示了仅由TBC1D21和LOXL1变异组合形成的独特单倍型结构，显示出对亚洲人群具有高XFS/XFG易感性。尽管在其他区域仍可能存在其他导致疾病发生过程的基因，但这些结果表明，这些基因中新发现变异的组合可能有助于精确的XFG风险评估，以及通过XFS阐明XFG发病机制的分子机制。
