The role of lysyl oxidase-like 1 DNA copy number variants in exfoliation glaucoma.

Purpose: To investigate whether DNA copy number variants (CNVs) in the lysyl oxidase-like 1 (LOXL1) gene are associated with exfoliation glaucoma (XFG) in black South Africans.

Methods: Black South African subjects with XFG and age-matched unaffected controls were recruited from the St. John Eye Hospital in Soweto (Johannesburg, South Africa) and East London Hospital Complex (Eastern Cape, South Africa) using standard clinical examination techniques. A customized array comparative genomic hybridization (aCGH) from Roche NimbleGen was designed to cover a 1.5 million base genomic region centered on the LOXL1 gene on chromosome 15. Twenty selected XFG cases were examined using this custom aCGH to identify common CNVs in the LOXL1 gene. The potential DNA copy number variants identified from aCGH were further validated using TaqMan probe-based CNV real-time PCR in a data set containing 91 XFG cases and 52 controls. The frequencies of CNVs in the LOXL1 region were compared between the XFG cases and the controls using Fisher's exact test.

Results: Several DNA CNV variants were identified in the LOXL1 genomic region using aCGH in the selected XFG cases. However, we were unable to validate these candidate CNVs using real-time PCR-based TaqMan CNV assays. There was no significant difference in the frequency of the DNA copy number variants in the LOXL1 region between the XFG cases and the controls.

Conclusions: This represents the first DNA CNV study of LOXL1 in the black South African population with XFG. Our study did not identify any significant DNA copy number alterations in the genomic region containing the LOXL1 gene. This suggests that other as yet unknown causal variants of LOXL1 or variants in other genes in linkage disequilibrium with the LOXL1 locus contribute to the genetic risk of XFG in black South Africans.