Importance: This study was necessary to establish the association between common genetic variants in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation (PEX) syndrome and emphasize the reversal of promoter risk allele in a South Indian population.
Objective: To investigate the potential association of genetic variants across the LOXL1 gene in South Indian patients with PEX syndrome and glaucoma.
Design, setting, and participants: A case-control study of individuals from Madurai, India, with PEX syndrome and glaucoma as well as healthy people serving as controls. Three hundred unrelated people with PEX syndrome and 225 age- and ethnically matched controls were recruited for genetic analysis.
Main outcomes and measures: Four single-nucleotide polymorphisms in LOXL1 (rs16958477, rs1048661, rs3825942, and rs2165241) were genotyped by direct sequencing in all participants. Regulatory regions and 7 coding exons of LOXL1 were directly sequenced in 50 patients and 50 controls. A case-control association analysis was performed using the Golden Helix SVS suite.
Results: An association between 4 LOXL1 single-nucleotide polymorphisms with PEX syndrome and glaucoma was observed (rs16958477, P = 4.77 × 10-6 [odds ratio, 0.50]; rs1048661, P = 4.28 × 10-5 [1.79]; rs3825942, P = 4.68 × 10-30 [9.19]; and rs2165241, P = 1.98 × 10-15 [2.88]). Sequencing of 7 exons and regulatory regions of LOXL1 identified 11 additional sequence variants; only rs41435250 showed an association (P = 3.80 × 10-5 [0.49]) with PEX syndrome and glaucoma.
Conclusions and relevance: Genetic variants in LOXL1 are associated with PEX syndrome and glaucoma in the South Indian population. To our knowledge, this is the first study to demonstrate the association of rs41435250 with PEX as well as reversal of the promoter risk allele. Understanding the role of the LOXL1 gene in PEX pathogenesis will facilitate early detection in individuals at risk for this condition.