New clinical classification and the evaluation of therapy for age-related macular degenerations based on the mutation of fibulin family genes.

点击翻译按钮获取中文摘要

1. Ninety-six cases of typical exdative age-related macular degeneration (AMID), 112 cases of polypoidal choroidal vasculpathy (PCV)and 153 controls were enrolled in this study.2. At the start of study, we found the latest report showing a negative correlation of fibulin gene with Japanese AMD. In addition, most recent studies of AMD genetics were being carried out using the analysis of single nucleotide polymorphism SNP), so we had to follow this direction.3. First, we investigated LOC387715/HTRA1 SNPs in Japanese population since these SNPs were recently found as the suggested risk factors of AMD.4. Risk alleles of LOC387715/HTRA1 were significantly more frequent in typical AMD and PCV groups than controls. The frequency of these risk alleles were not significantly different between typical AMD and PCV groups.5. Homozygous risk allele of HTRA1 gene showed odds ratios as 6.3 in PCV and 13.8 in typical AMD groups compared to controls.Heterozygous risk allele showed odds rations as 2.5 in PCV and 7.4 in typical AMD.6. We next looked at the SNPs of elastin gene and found that homozygous risk allele in rs2301995 showed a significant increase of susceptibility for PCV with odds ratio of 7.6 compared to control. Haplotype analysis also showed a significant difference between PCV and control (odds ratio 2.1), while no difference was found between typical AMD and control. This is the first report which demonstrates the genetic risk factor of PCV.7. There were significant differences in single SNP of rs2301995 and haplotype of elastin gene between typical AMD and PCV, which indicates the different genetic background of these phenotypes of AMD.