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

Abstract

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 keratoconus in Korean patients, we investigated the associations of single nucleotide polymorphisms (SNPs) in these three genes in Korean patients 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 genes were directly sequenced to determine the presence of mutations. Control individuals were selected from the general population without 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 patient and control groups. In the SPARC gene, the distribution of the *G allele of EX10+225 T>G ( p = 0.018; odds ratio, 1.869) was strongly associated with the risk of keratoconus in the Korean population. In haplotype analysis, C-G of rs2956540-rs2288393 in 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 permutation tests, 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 predisposition for keratoconus in Korean individuals. Moreover, variations in ALDH3A1 and LOX may serve as strong biomarkers for keratoconus.

Common ALDH3A1 Gene Variant Associated with Keratoconus Risk in the Polish Population

“…However, two preliminary results from the Polish [ 20 ] and Korean populations [ 21 ] suggested an association of ALDH3A1 variants with KC risk. The preliminary data from the Korean population were confirmed recently and the rs2228100 variant of ALDH3A1 was found to be strongly associated with KC risk [ 22 ].…”

“…This study is an extension of our results presented at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting 2016 [ 20 ] for reporting the first time an association has been found of ALDH3A1 variants with KC in Poles. In addition, a recent study of the Korean population reported such an association (rs2228100 strongly associated with KC risk) [ 22 ].…”

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus

“… 15 , 21 , 52 , 53 The rs2956540 and rs10519694 are 2 well-known SNPs found in the fourth intron of the LOX gene and connected to KC in different populations. 8 , 12 , 29 , 54 …”

Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus

“…Although OMIM links the gene to autosomal recessive osteogenesis imperfecta, missense variants in SPARC have been detected in patients with keratoconus, so the involvement of the gene in the pathology is possible. In addition, the proximal location of SPARC to the LOX gene, residing on chromosomes 5q31.3-q32 and 5q23.2, respectively, could also suggest its contribution to keratoconus [58]. A third variant in heterozygosis appears in the TTN gene (p.(Val24529Leu)), whose relationship with KC is argued in the OFT-00814 family [40].…”