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

1.入组典型发育性老年性黄斑变性(AMID)96例，息肉状脉络膜血管病(PCV)112例，对照组153例。在研究开始时，我们发现最新的报告显示菲布林基因与日本AMD呈负相关。另外，最近对AMD遗传学的研究大多采用单核苷酸多态分析(SNP)，因此我们必须遵循这一方向。首先，我们调查了日本人群中的LOC387715/HTRA1 SNPs，因为这些SNP是最近被发现的AMD.4的潜在危险因素。在典型AMD组和PCV组中，LOC387715/HTRA1等位基因频率显著高于对照组。这些危险等位基因在典型AMD组和PCV组之间的频率差异无统计学意义。与对照组相比，HTRA1基因纯合风险等位基因在PCV中的优势比为6.3，在典型AMD组中的优势比为13.8，杂合子风险等位基因在PCV中的优势比为2.5，在典型AMD中的优势比为7.4。我们接下来研究了弹性蛋白基因的SNPs，发现rs2301995中的纯合子风险等位基因显示出与对照组相比PCV的易感性显著增加，优势比为7.6。单倍型分析也显示PCV组和对照组有显著差异(优势比2.1)，而典型AMD组和对照组之间没有差异。这是第一份证明PCV.7的遗传风险因素的报告。典型AMD与PCV的rs2301995单核苷酸多态和弹性蛋白基因单倍型存在显著差异，提示不同表型的AMD具有不同的遗传背景。

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.