Absence of significant genetic alterations in the VSX1, SOD1, TIMP3, and LOX genes in Brazilian patients with Keratoconus.

PURPOSE: To identify inherited or acquired mutations in the VSX1, SOD1, TIMP3 and LOX genes from the combined analysis of corneal and blood samples from patients with Keratoconus. METHODS: The casuistry was consisted of samples of peripheral blood and corneal epithelium from 35 unrelated patients with Keratoconus who were submitted to corneal crosslink treatment. Also, blood and corneal epithelium samples from 89 non-keratoconic patients were used to compose the control group. Ophthalmologic evaluations included a clinical examination, topography and tomography. DNA samples were extracted from peripheral blood and from corneal epithelium in both groups and all coding regions of the VSX1, SOD1, TIMP3 and LOX genes were amplified by polymerase chain reaction, denatured and subjected to polyacrylamide gel electrophoresis. Mutational screening was performed by single-strand conformation polymorphism and direct DNA sequencing. RESULTS: No pathogenic variant was found in all coding regions of VSX1, SOD1, TIMP3 and LOX genes, we detected only few SNPs (single-nucleotide polymorphisms). Among the polymorphisms stand out three of them, corresponding to the synonymous exchange of amino acids: exon 3 of VSX1 Ala182Ala and exon 3 of TIMP3 His83His and Ser87Ser; in patients with Keratoconus and also in control subjects. All the polymorphisms were found in samples of corneal epithelium and corresponding blood. CONCLUSION: There is absence of KC pathogenic related to mutations in the VSX1, SOD1, TIMP3 and LOX genes in the studied patients.

Influence of interleukin 17 A and 17 F polymorphisms in keratoconus.

BACKGROUND: Until a few years ago, keratoconus was defined as a noninflammatory degenerative disease. However, recent studies have shown that the altered balance between inflammatory cytokines, proteases, and protease inhibitors, as well as free radicals and oxidants, have a crucial role in the pathogenesis of this disease. The aim of this study is to investigate whether interleukin 17 A G197A (rs2275913) and interleukin 17 F T7488C (rs763780) polymorphisms are associated with keratoconus in patients from a population of the northwestern region of the State of São Paulo, Brazil. METHODS AND RESULTS: 35 patients and 61 controls were enrolled. Genotyping of interleukin 17 A G197A and interleukin 17 F T7488C polymorphisms was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical analyses were conducted using the chi-square test, and an odds ratio with a 95% confidence interval was also calculated to evaluate the association between polymorphisms and disease. Evaluating interleukin 17 F T7488C, we found that the TT genotype is associated as a risk factor for keratoconus (P = 0.04; OR = 3.01; CI 1.11-8.14). As for evaluating interleukin 17 A G197A, the allele and genotype frequencies between patients and controls were compared and no statistically significant differences were found. CONCLUSIONS: Our data showed that the interleukin 17 F T7488C polymorphisms may exert an influence in keratoconus.