Mori Kazuhiko, Imai Kojiro, Matsuda Akira, Ikeda Yoko, Naruse Shigeta, Hitora-Takeshita Hisako, Nakano Masakazu, Taniguchi Takazumi, Omi Natsue, Tashiro Kei, Kinoshita Shigeru
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mol Vis. 2008 Jun 5;14:1037-40.
We performed genetic association studies using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. We also quantified LOXL1 mRNA expression in the human lens capsule to examine the possible correlation between LOXL1 expression and XFG pathogenesis.
We performed a case-control study using 95 Japanese XFG patients and 190 controls. Real-time polymerase chain reaction (PCR) analysis was performed using lens capsules obtained during surgery.
The TT genotype in the single nucleotide polymorphism (SNP) rs1048661 and the GG genotype in the SNP rs3825942 in exon 1 of LOXL1 were significantly associated with an increased risk of XFG under recessive models (chi(2) test, p=5.34 x 10(-34) and p=2.1 x 10(-8), respectively). Quantification of LOXL1 mRNA expression demonstrated no significant difference between XFG and senile cataract samples.
Although the functional effects of the LOXL1 SNP appear to be qualitative rather than quantitative, the amino acid substitution (R141L) caused by SNP rs1048661 is not a simple decisive factor for XFG due to the inverted allele frequency between Japanese XFG and Caucasian XFG patients. Further genetic and functional studies are essential for clarifying XFG pathogenesis.
我们使用日本本土人群进行了基因关联研究，以检验赖氨酰氧化酶样1（LOXL1）基因关联研究结果在剥脱性青光眼（XFG）中的可重复性，而不考虑种族差异。我们还对人晶状体囊膜中的LOXL1 mRNA表达进行了定量分析，以研究LOXL1表达与XFG发病机制之间可能存在的相关性。
我们对95例日本XFG患者和190例对照进行了病例对照研究。使用手术中获取的晶状体囊膜进行实时聚合酶链反应（PCR）分析。
在隐性模型下，LOXL1第1外显子单核苷酸多态性（SNP）rs1048661中的TT基因型和SNP rs3825942中的GG基因型与XFG风险增加显著相关（卡方检验，p分别为5.34×10⁻³⁴和2.1×10⁻⁸）。LOXL1 mRNA表达定量分析显示，XFG样本和老年性白内障样本之间无显著差异。
尽管LOXL1 SNP的功能效应似乎是定性而非定量的，但由于日本XFG患者和白种人XFG患者之间等位基因频率相反，SNP rs1048661导致的氨基酸替代（R141L）并非XFG的简单决定性因素。进一步的基因和功能研究对于阐明XFG发病机制至关重要。
