Genetics in exfoliation syndrome and age‐related cataract

Abstract

Abstract Purpose To describe the recent discovery of the association of Lysyl Oxidase Like 1 (LOXL1) gene polymorphisms with exfoliation syndrome as well as similar study on age‐related cataract. Methods For phenotyping of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) peripheral band and/or central shield of exfoliative material on the anterior lens capsule was required and in case of glaucoma glaucomatous optic neuropathy. For phenotyping we excluded all exfoliation suspects. The phenotyping of cataract included cortical and nuclear cataract by type and grade using the Japanese Co‐operative Cataract Epidemiology Study Group system. Our genome wide association study on open angle glaucoma included XFG. For both studies we used the Illumina 300 chip including over 300,000 single – nucleotide polymorphisms (SNP´s). Results When we had done 195 open angle glaucoma cases high genome wide significance was achieved on chromosome 15q24.1 in the LOXL 1 gene, later identified to be confined to XFG only. Combined, the identified DNA sequence variants explained 99% of the population attributable risk for exfoliation glaucoma. Having done 234 cases of age‐related cataract we still have not achieved a high genome wide significance although there was a modest signal associated with the LOXL1 polymorphisms. Conclusion Exfoliation glaucoma and age‐related cataract have in twin studies both been found to have strong hereditary components. We did discover a major genetic risk factor for XFG/XFS, have however, so far, been unable to identify a highly significant single nucleotide polymorphism for age‐related cataract. The risk factors for cataract may include many modest genetic risk factors together with environmental risk factors.