Association with Corneal Remodeling Related Genes, ALDH3A1, LOX, and SPARC Genes Variations in Korean Keratoconus Patients

Purpose: To determine whether the cornea remodeling-related genes aldehyde dehydrogenase 3A1 (ALDH3A1), lysyl oxidase(LOX), and secreted protein acidic and rich in cysteine (SPARC) were potential susceptibility candidate genes for keratoconusin Korean patients, we investigated the associations of single nucleotide polymorphisms (SNPs) in these three genes in Koreanpatients with keratoconus. Methods: Genomic DNA was extracted from blood samples of unrelated patients with keratoconus and healthy control individuals. For screening of genetic variations, all exons from the entire coding regions of the ALDH3A1, LOX, and SPARC geneswere directly sequenced to determine the presence of mutations. Control individuals were selected from the general populationwithout keratoconus. Results: In this study, we detected nine SNPs in ALDH3A1, four SNPs in LOX, and 18 SNPs in SPARC. rs116992290, IVS3-62c>t,rs116962241, and rs2228100 in ALDH3A1 and rs2956540 and rs1800449 in LOX were significantly different between patientand control groups. In the SPARC gene, the distribution of the *G allele of EX10+225 T>G (p = 0.018; odds ratio, 1.869) wasstrongly associated with the risk of keratoconus in the Korean population. In haplotype analysis, C-G of rs2956540-rs2288393in LOX (p = 0.046) and C-C-G and G-G-G of rs60610024-rs2228100-rs57555435 (p = 0.021 and p < 0.001), G-A of IVS3-62 a>g- rs116962241 in ALDH3A1 (p = 0.048) predisposed significantly to keratoconus. After cross-validation consistency and permutationtests, two locus model was the best SNP variations interaction pattern. Conclusions: Our results suggested that genetic variations in ALDH3A1, LOX, and SPARC genes were associated with a predispositionfor keratoconus in Korean individuals. Moreover, variations in ALDH3A1and LOX may serve as strong biomarkers forkeratoconus.