Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amino Acid Oxidoreductases / genetics*
  • Asian People / genetics
  • Exfoliation Syndrome / ethnology
  • Exfoliation Syndrome / genetics*
  • Female
  • GTPase-Activating Proteins / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / statistics & numerical data
  • Haplotypes*
  • Humans
  • Japan
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Promyelocytic Leukemia Protein
  • Risk Factors
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics


  • GTPase-Activating Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • TBC1D21 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human