Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population

Abstract

BackgroundKeratoconus (KC) is the most common primary ectatic disease of the cornea and a major indication for corneal transplant. To date, limited KC-associated-risk loci have been identified. Association has recently been suggested between KC and 8 single nucleotide polymorphisms (SNPs) in the genomic regions of FNDC3B, COL4A3, MPDZ-NF1B, RXRA-COL5A1, LCN12-PTGDS, FOXO1, and BANP-ZNF469. These SNPs are associated with central corneal thickness (CCT), a known risk factor to KC. We are questioning whether these SNPs are significantly associated with KC in a Saudi Arabian population. The study included 108 unrelated KC cases and 300 controls. Patients were diagnosed with KC according to the Schimpff-flow based elevation map of the cornea. DNA genotyping was done using probe-based allelic discrimination TaqMan assays. Allele frequencies were compared between the cases and controls.ResultsAll SNPs were successfully genotyped with high efficiency (>95 %). The SNPs had no significant deviation in cases or controls from Hardy-Weinberg Equilibrium (HWE, p value > 0.05). None of the selected SNPs were significantly associated with KC in the Saudi Arabian population. However, we replicated the same trend of minor allele frequency (MAF) between cases and controls reported by a recent GWAS regarding the 5 SNPs rs4894535 (FNDC3B, chr3: 171995605), rs1536482 (RXRA-COL5A1, chr9: 137440528), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264), and rs2721051 (FOXO1, chr13: 41110884).ConclusionsThis is the first study investigating the association of these SNPs with KC in a population from Saudi Arabia. We replicated the same trend of MAF alteration of the association between the SNPs rs4894535 (FNDC3B, chr3: 171995605), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264) and rs2721051 (FOXO1, chr13: 41110884) and KC-risk as reported by a recently published GWAS. Consistently replicated population-based studies are necessary to identify and/or confirm genetic susceptibility for certain diseases. We acknowledge that the lack of significance in our study is due to our small sample size and insufficient statistical power; however our data still add to the body of evidence of potential KC-candidate SNPs. This report aims at supporting the possible association between CCT-associated SNPs and KC susceptibility.

Genetics in Keratoconus: where are we?

“…Genes coding for collagens COL4A3 (type IV collagen alpha3, COL4A4 (type IV collagen alpha4) have been suggested as well [ 123 , 124 ]; however, additional studies in multiple populations found no association with these SNPs [ 91 , 125 ] or found evidence of their extensive presence in the normal population [ 126 ].…”

Molecular Genetics of Keratoconus: Clinical Implications

“…In a Han Chinese cohort of 210 patients and 191 controls in northern China, the association was p = 0.005, OR = 3.1 [115]. However, no association was found in a Saudi Arabia study of 108 patients and 300 controls [116]. In contrast, very high risk of rs1324183 to keratoconus, P = 4.30 × 10 −4 OR = 2.22 was shown after genotyping of 133 patients and 367 controls who are Han Chinese in Hong Kong in southern China [117].…”

Lamellar keratoplasty in a referral center in northeastern Brazil

“…Such condition is developed during [10] About this corneal vascularization in 22.22% (n=4) of the cases, it is a factor that should be considered to be one of the complications of DALK due to surface and suture changes. Thus, a history of anterior vascular keratoplasty could represent a triggering factor for corneal opacification [11].…”