Polimorfismo genético em pacientes portadores de ceratocone

• Autor(a) principal: Rodrigues, Francisco Weliton
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/7065
• topic: Ceratocone; Córnea; Mutação; qPCR; DNA; Keratoconus; Cornea; Mutation; qPCR; DNA; CIENCIAS DA SAUDE::ODONTOLOGIA

Keratoconus is a chronic non-inflammatory ocular disorder characterized by central thinning, protrusion and conical shape of the cornea. The progression of this disorder cause a significant decrease in visual acuity. It has been suggested that the development of keratoconus has a genetic component. Therefore, the aim of this study was to evaluate the frequency of single nucleotide polymorphisms (SNP) mutations associated with keratoconus in unrelated Brazilian patients compared to healthy subjects. This was a case-control clinical study with 108 participants, 46 patients with keratoconus and 62 healthy subjects (controls). Peripheral blood, collected from all participants, was used to extract DNA samples. Subsequently, genotyping of three single nucleotide polymorphisms, TGFBI rs4669 and rs2072239 and VSX1 rs6138482, was performed through real-time polymerase chain reactions (qPCR). Single nucleotide polymorphisms were observed in both keratoconus patients and healthy subjects. For the VSX1 gene, allelic frequency and discrimination was similar for keratoconus patients and controls. Conversely, the frequency of the mutant allele was significantly higher for two SNPs on the TGFBI gene in patients with keratoconus. For the SNP rs4669, the patients with keratoconus had 15 % higher frequency of the mutated allele, while for the SNP rs2072239 the patients had 11 % higher frequency of the mutated allele compared to the controls. Individuals carrying the mutant allele had two-times more risk in developing the disease. The allelic discrimination of genotypes (homozygous and heterozygous) was also significantly different for both SNPs on the TGFBI gene. This study has demonstrated, for the first time, an association of SNP mutations and the development of keratoconus in Brazilian patients. The frequency of the mutant and potentially pathogenic allele on the TGFBI gene was significantly higher in patients compared to controls. Finally, these findings contribute to the advance of molecular knowledge of the pathogenesis, development of early diagnostic tools and therapeutics options for patients with keratoconus.