Polymorphism Analysis ofVSX1andSOD1Genes in Greek Patients with Keratoconus

Abstract

We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the pathogenesis of KC. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of KC.

The Genetic Background of Keratoconus: A Review on Keratoconus Genes

“…R166W and H244R VSX1 variants might play critical role in the pathogenesis of keratokonic corneas, as suggested by SaeeRad et al [53]. The same study group identified three novel SNPs (g. 4886G>A, g.4990C>G, and g.9061T>A) in SOD1, but these SNPs did not seem to influence the activity of SOD1 protein [53]. Czugala et al detected four substitutions in three different genes: c.2262A>C (p.Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in Serine/threonine-protein kinase (STK24) [54].…”

“…However, in the same study the SOD1 intronic 7-base deletion (c.169 + 50delTAAACAG) was over-represented among keratoconic patients compared to healthy controls [52]. R166W and H244R VSX1 variants might play critical role in the pathogenesis of keratokonic corneas, as suggested by SaeeRad et al [53]. The same study group identified three novel SNPs (g. 4886G>A, g.4990C>G, and g.9061T>A) in SOD1, but these SNPs did not seem to influence the activity of SOD1 protein [53].…”

Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil

“…To test for the presence of the intronic 7-base deletion IVS2 + 50del7bp (c.169+50delTAAACAG) in SOD1, samples were tested by PCR in 140 KC positive patients and 120 controls, using previously described amplification conditions. [29] Detection of this deletion in patients involved direct visualization of a 211 bp amplicon in a 20 x 20 cm PAGE (5%) electrophoresis, followed by confirmatory DNA sequencing of positive samples.…”

“…[26] Several studies have described a heterozygous genomic 7-base deletion in the intron 2 of the SOD1 gene (IVS2 + 50del7bp) in the US population which significantly affected the conformation and function leading to an increase in oxidative stress in the cornea. [27][28][29] Two sporadic carriers of this deletion were also detected in the Italian population, [30] and nine in the Greek population. [29] The involvement of SOD1 in other ocular diseases such as primary open-angle glaucoma has also been described.…”

“…[27][28][29] Two sporadic carriers of this deletion were also detected in the Italian population, [30] and nine in the Greek population. [29] The involvement of SOD1 in other ocular diseases such as primary open-angle glaucoma has also been described. [31] Although already well studied, [32,33] the genetic basis of KC is still poorly understood.…”