Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations

Hum Genomics. 2012 Oct 10;6(1):22. doi: 10.1186/1479-7364-6-22.


Pseudoexfoliation syndrome (PXS) is a systemic condition with eye manifestations. In the eye, pseudoexfoliation material deposits on various structures of the anterior segment. The nature of this material is mostly fibrillar with fibers made up of microfibrils and coated with amorphous material. The composition of these fibrils is diverse and includes basement membrane components as well as enzymes involved in extracellular matrix maintenance. Pseudoexfoliation is the most common cause of secondary open-angle glaucoma (pseudoexfoliation glaucoma, PXG) worldwide. The goal of this review is to summarize our knowledge on the genetics of this systemic disorder and its resultant ocular manifestations. PXS familial aggregation suggests genetic inheritance. PXS has been strongly associated with single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like 1 (LOXL1) gene on chromosome 15q24.1. Two of these SNPs confer a higher than 99% population attributable risk for PXS and PXG in the Nordic population; however, they carry different risks in different populations. The high risk haplotypes also vary among different populations. LOXL1 is one of group of the enzymes involved in the cross-linking of collagen and elastin in the extracellular matrix. Its function in connective tissue maintenance has been confirmed in mice; however, its actual role in PXS remains unclear. Contactin-associated protein-like 2 also has a strong genetic association with PXS in a German cohort and is an attractive candidate molecule. It encodes for a protein involved in potassium channel trafficking. Other candidate genes linked to PXS include lysosomal trafficking regulator, clusterin, adenosine receptors, matrix metalloproteinase-1 (MMP1), and glutathione transferase. These genes may be modifying genes for development of PXS and PXG.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Oxidoreductases / genetics*
  • Chromosomes, Human, Pair 15 / genetics*
  • Clusterin / genetics
  • Collagen / genetics
  • Elastin / genetics
  • Exfoliation Syndrome / genetics*
  • Exfoliation Syndrome / physiopathology
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Eye / physiopathology
  • Gene-Environment Interaction
  • Glaucoma, Open-Angle / genetics
  • Glaucoma, Open-Angle / physiopathology
  • Glutathione Transferase / genetics
  • Haplotypes
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • Polymorphism, Single Nucleotide
  • Receptor, Adenosine A3 / genetics


  • Clusterin
  • Receptor, Adenosine A3
  • Collagen
  • Elastin
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human
  • Glutathione Transferase
  • MMP1 protein, human
  • Matrix Metalloproteinase 1