Lysyl-oxidase-like 1 gene polymorphism in Japanese patients with primary open-angle glaucoma and exfoliation glaucoma

Department of Ophthalmology, University of Yamanashi, Yamanashi, Japan.
Molecular vision (Impact Factor: 1.99). 07/2008; 14:1303-8.
Source: PubMed

ABSTRACT To assess whether lysyl oxidase-like 1 (LOXL1) polymorphisms are associated with primary open-angle glaucoma (POAG) and exfoliation syndrome (XFS).
Japanese patients with POAG (n=213) or XFS (n=89) and 191 control subjects were analyzed for LOXL1 polymorphisms (rs1048661: 758G/T, Arg141Leu and rs3825942: 794G/A, Gly153Asp). Demographic and clinical features of POAG patients and control subjects were compared in terms of the TT/GG compound genotype of rs1048661 and rs3825942.
There was a significant difference in the genotype frequencies between XFS patients and control subjects (p<0.0001). Frequencies of the T allele of rs1048661 and the G allele of rs3825942 were significantly higher in XFS patients than in control subjects (rs1048661: 99.4% versus 55.0%; rs3825942: 99.4% versus 85.3%; p<0.0001). Except for one who had the TG/AG compound genotype, all XFS patients had the TT/GG compound genotype. An almost 250 fold increase in the risk of XFS (p<0.0001; odds ratio: 252.2; 95% confidence interval: 32.7 to more than 1000) was found in patients with the TT/GG compound genotype compared to those without the genotype. There were no significant differences in the genotype and allele frequencies between POAG patients and control subjects. Furthermore, no significant differences were noted in the demographic and clinical features of POAG patients as well as control subjects with and without the TT/GG high-risk compound genotype.
LOXL1 polymorphisms were associated with XFS. However, the frequencies of the polymorphisms differed between Japanese and Caucasian XFS patients. These polymorphisms had no influence on the phenotypic features of POAG patients.

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Available from: Yoichi Sakurada, Sep 27, 2015
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    • "However, LOXL1, in and of itself, fails to sufficiently explain the complex mechanism of the disease progression of XFG through XFS. This observation is also supported from the point of view of genetics, as many replication studies using populations derived from different genetic backgrounds (Caucasians from the US789 and Europe1011, Asians from Japan1213141516 and China1718, and Africans from South Africa19) have succeeded in replicating the association of the LOXL1 variants, although the allele frequency of the variants varied among the ethnicities. In fact, the risk allele of one of the exonic variants (rs1048661) has been found to be inverted between Japanese12 and Nordic populations5. "
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    ABSTRACT: 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.
    Scientific Reports 06/2014; 4:5340. DOI:10.1038/srep05340 · 5.58 Impact Factor
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    • "No significant association was found between LOXL1 variants and POAG in previous studies [9,18,21,27-29]. This finding was verified in our study population. "
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    ABSTRACT: To investigate the association of lysyl oxidase like 1 (LOXL1) variants with exfoliation syndrome (XFS), exfoliation glaucoma (XFG), and primary open angle glaucoma (POAG) in a Turkish population. Two LOXL1 single nucleotide polymorphisms (SNPs), rs1048661 (R141L) and rs3825942 (G153D), were analyzed in 300 Turkish patients (100 patients with XFS, 100 patients with XFG, 100 patients with POAG) and 100 control subjects. The T allele of rs1048661 was underrepresented in patients with XFS (odds ratio [OR]=0.334, 95% confidence interval [CI]: 0.198-0.564, p=2.54×10(-5)) and XFG (OR=0.366, 95% CI: 0.219-0.611, p=8.56×10(-5)) compared to the control subjects. None of the patients with XFS or XFG had the A allele of rs3825942, whereas 16% of the control subjects had that variant (OR=0.025, 95% CI: 0.003-0.188, p=3.69×10(-9)). No association was observed between the SNPs studied and POAG. By using logistic regression analysis, the effect of rs1048661 remained significant (p=8.45×10(-8)) after controlling for the effect of rs3825942, whereas rs3825942 was not significant with conditioning on rs1048661. Female gender was protective against the disease controlling with the effect of the two SNPs (OR=0.527, 95% CI: 0.358-0.776, p=0.001). The findings of the current study indicate that in a logistic regression analysis model the T allele of rs1048661 is the most important risk-modifying factor for the development of XFS and XFG. Our results also confirm in a Turkish population the findings of previous reports describing the association between LOXL1 polymorphisms and XFS/XFG but not with POAG. The allele and genotype distribution in this cohort appear to be similar to those of Caucasians.
    Molecular vision 01/2013; 19:114-20. · 1.99 Impact Factor
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    • "genetic contribution for POAG seems to be a complex. In EG, SNPs were highly significant on a single gene, LOXL1, by GWAS (Thorleifsson et al. 2007; Williams et al. 2010; Mabuchi et al. 2008; Fan * Correspondence: "
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    ABSTRACT: Primary open-angle glaucoma (POAG) is one of the major causes of blindness worldwide and considered to be influenced by inherited and environmental factors. Recently, we demonstrated a genome-wide association study for the susceptibility to POAG by comparing patients and controls. In addition, the serum cytokine levels, which are affected by environmental and postnatal factors, could be also obtained in patients as well as in controls, simultaneously. Here, in order to predict the effective diagnosis of POAG, we developed an "integration approach" using different attribute data which were integrated simply with several machine learning methods and random sampling. Two data sets were prepared for this study. The one is the "training data set", which consisted of 42 POAG and 42 controls. The other is the "test data set" consisted of 73 POAG and 52 controls. We first examined for genotype and cytokine data using the training data set with general machine learning methods. After the integration approach was applied, we obtained the stable accuracy, using the support vector machine method with the radial basis function. Although our approach was based on well-known machine learning methods and a simple process, we demonstrated that the integration with two kinds of attributes, genotype and cytokines, was effective and helpful in diagnostic prediction of POAG.
    SpringerPlus 10/2012; 1:41. DOI:10.1186/2193-1801-1-41
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