Association of Lysyl oxidase (LOX) polymorphisms with the risk of Keratoconus in an Iranian population

Background: Keratoconus is a connective tissue-related eye disease with unknown etiology that causes the loss of visual acuity. Lysyl oxidase (LOX) is an amine oxidase that catalyzes the covalent cross-link of collagens and elastin in the extracellular environment, thus determining the mechanical properties of connective tissue. The current study aimed to investigate the possible associations between two LOX polymorphisms, rs1800449 and rs2288393, and susceptibility to keratoconus.

Methods: A total of 262 Iranian subjects including 112 patients with keratoconus and 150 healthy individuals as controls were recruited. Genotyping for the LOX variants was performed using allele-specific PCR.

Results: A significant difference was found between two groups regarding allelic and genotyping distribution of LOX polymorphism at position rs1800449 G>A. The frequency of AA and GA + AA genotypes were increased in patients compared to controls (17% versus 8% and 62.5% versus 50%, respectively), showing a statistically significant difference (OR = 2.827, 95% CI: 1.251–6.391, p = 0.012). The A allele was associated with an increased risk for keratoconus, with the frequency of 39.9% and 29% in patients and controls, respectively (OR = 1.614, 95% CI: 1.119–2.326, p = 0.011). Furthermore, the haplotype analysis revealed that the rs1800449G/rs2288393C is a protective factor against keratoconus (OR = 0.425, 95% CI = 0.296–0.609, p = 0.001). Conversely, the +473A/rs2288393C (OR = 3.703, 95% CI = 2.230–6.149, p = 0.001) and +473G/rs2288393G (OR = 15.48, 95% CI = 3.805–63.03, p = 0.001) haplotypes were identified as risk factors for keratoconus.

Conclusion: Our study demonstrated that the LOX rs1800449 genotypes (AA and GA + AA) and allele (A) appears to confer risk for susceptibility to keratoconus.